Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (>1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have severe impact on the patient’s quality of life. The current review summarizes evidence for utility of amantadine in TBI in connection to its mechanism of action. Amantadine combining multiple mechanisms of action may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as infusion which may be of particular benefit in unconscious patients with TBI, due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: Can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers these questions.

A Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damages induced by repetitive injuries occurring in the brain are more common, especially amongst athletes. rmTBI can also have a detrimental effect on the retina and the pathophysiology of these injuries are likely to differ from the severe TBI (sTBI) retinal injury.Here we showed how rmTBI and sTBI can dissimilarly affect the retina. Our results indicate an increase in the number of activated microglial cells and Caspase3-positive cells in the retina in both traumatic models, suggesting a rise in the level of inflammation and cell death after TBI. The pattern of microglial activation appears evenly distributed and widespread but differs amongst the various retinal layers. sTBI induced microgial activation in both the superficial and deep retinal layers. In contrast to sTBI, no significant change occurred following the repetitive mild injury in the superficial layer, only the deep layer (spanning from the inner nuclear layer to the outer plexiform layer) shows microglial activation. This difference suggests that alternate response mechanisms play a role in the case of the different TBI incidents. The Caspase3 activation pattern showed a uniform increase in both the superficial and deep layers of the retina. This suggests a different action in the course of the disease in sTBI and rmTBI models and points to the need for new diagnostic procedures.Our present results suggest that the retina might serve as such a model of head injuries since the retinal tissue reacts to both forms of TBI and is the most accessible part of the human brain.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

. Background: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. Methods: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical, functional details (“Glasgow Outcome Scale – Extended”, “Functional Independent Measure”, Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. Results: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability to be partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working –taking into account limitations due to the traumatic event, versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. Conclusions: Rehabilitation should adequately emphasize “vocational rehabilitation” because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with moderate/severe TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust structural brain measures with relevance for improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study pro-vides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Head trauma or any traumatic injury can cause damage to parts of the brain. The most important part regulating the body are the hormones and the two centers of brain which are main ones for this regulation are the most prone to getting injured. The hypothalamus and pituitary regulate a lot many functions and the loss of these organs can cause Adrenal Insufficiency, SIADH, Diabetes Insipidus, and many more.

We tested the hypothesis that obesity influences the pharmacodynamics of volatile general anesthetics (VGAs) by comparing effects of anesthetic exposure on mortality from traumatic brain injury (TBI) in lean and obese Drosophila melanogaster. We induced TBI with a High-Impact Trauma device. Starvation-selection over multiple generations resulted in an obese phenotype (SS flies). Fed flies served as lean controls (FC flies). Adult (1-7 day old) SS and FC flies were exposed to equianesthetic doses of isoflurane or sevoflurane either before or after TBI. The principal outcome was percent mortality 24 hours after injury, expressed as the Mortality Index at 24 hours (MI24). TBI resulted in lower MI24 in FC than in SS flies (21 (2.35) and 57.8 (2.14), respectively n= 12, p=0.0001). Preexposure to isoflurane or sevoflurane preconditioned FC flies to TBI reducing the risk of death to 0.53 [0.25 to 1.13] and 0.82 [0.43 to 1.58], respectively, but had no preconditioning effect in SS flies. Postexposure to isoflurane or sevoflurane increased the risk of death in SS flies. Only postexposure to isoflurane increased the risk in FC flies (1.39 [0.81 to 2.38]). Thus, obesity affects the pharmacodynamics of VGAs, thwarting the preconditioning effect of isoflurane and sevoflurane in TBI.

Emotion recognition and social inference impairments are well-documented post-traumatic brain injury (TBI) yet the mechanisms underpinning these are not fully understood. We examined dynamic emotion recognition, social inference abilities, and eye fixation patterns between adults with and without TBI. Eighteen individuals with TBI and 18 matched non-TBI participants were recruited and underwent all three components of The Assessment of Social Inference Test (TASIT). The TBI group were less accurate in identifying emotions compared to the non-TBI group. Individuals with TBI also scored lower when distinguishing sincere and sarcastic conversations but scored similarly to those without TBI during lie vignettes. Finally, those with TBI also had difficulty understanding the actor’s intentions, feelings, and beliefs compared to participants without TBI. No group differences were found for eye fixation patterns and there were no associations between fixations and behavioural accuracy scores. This conflicts with previous studies and might be related to an important distinction between static and dynamic stimuli. Visual strategies appeared goal- and stimulus-driven, with attention being distributed to the most diagnostic area of the face for each emotion. These findings suggest that low-level visual deficits may not be modulating emotion recognition and social inference disturbances post-TBI.

Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in-vivo CD-1 mice. Further, we identified dysregulated NFB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. Finally, we found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy of bone marrow cells and activated NFB signaling genes in bone marrow-derived cells. Taken together, we provide evidence that TBI-induced inflammatory stress on bone and the bone marrow niche may activate NFB leading to accelerated bone loss. Targeted inhibition of these signaling pathways may reverse TBI-induced bone loss and reduce fracture rates.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.

Background: This review aims to explore the regulatory mechanism of microglial exosomes, particularly focusing on the role of miR-124-3p, in modulating neuroinflammation and promoting neuronal repair following traumatic brain injury (TBI). Methods: Multiple studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. The increased expression of miR-124-3p in microglial exosomes after TBI inhibited neuronal inflammation and promoted neurite outgrowth. This effect was achieved by promoting the anti-inflammatory M2 polarization of microglia, suppressing mTOR signaling through downregulation of PDE4B, and inducing autophagy in BMVECs. These actions collectively contributed to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. Conclusion: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. Targeting miR-124-3p and utilizing microglial exosomes as therapeutic agents hold great potential for future clinical translation in TBI management. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Background: Alongside their long-term effects - post-concussion syndrome (PCS) - mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. This study aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. Methods: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. Results: Studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS, as well as with repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. Conclusion: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and to develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p<0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Treating a patient with traumatic brain injury requires an interdisciplinary approach because of the pervasive, profound and protean manifestations of this condition. In this review, key aspects of the medical history and review of systems will be described in order to highlight how the role of any provider must evolve to become a better patient advocate. Although this review is written from the vantage point of a vision care provider, it is hoped that patients, caregivers and providers will recognize the need for the team approach; it truly takes a village.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of laminin and collagen IV within the ECM of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. Results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats the pattern was broken into aggregated granule-like immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra-and ipsilateral side of the TBI rats. However, in TBI rats most of the muscles from the contralateral hindlimb showed a significant increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: Retrospective review of electronic medical records from single rehabilitation unit was conducted from 1 Jan 2012 to 31 Dec 2014. Inclusion criteria were first TBI, aged >18 years, admitted < 6 months of TBI. ACUR were characterized into either of neurological, medical or neurosurgical subtypes. The main outcome measure was discharge Functional Independence Measure (FIM). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n=17), comprising neurologic (76.5%) and medical (23.5%) subtypes, occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs FIM ACUR-positive 50.53(25.4), P =0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs FIM ACUR-negative 85.4 (21.1), P = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts [ACUR-positive median 55 days (IQR 34.50, 87.50) vs ACUR-negative median 28 days (IQR 16.25, 40.00), P = 0.002]. Conclusion: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI.

Aims: Anxiety, major depressive disorder and accelerated cognitive decline frequently complicate traumatic brain injury. Obesity and type 2 diabetes mellitus drive peripheral inflammation which can accelerate traumatic brain injury-associated neurodegeneration. The Zucker rat harbors G-protein coupled receptor agonist IgG autoantibodies and in vitro neurotoxicity caused by these autoantibodies was prevented by a novel synthetic fragment of the serotonin 2A receptor. The aim of the present study was to test whether genetic obesity manifested in Zucker diabetic fatty rat is associated with anxiety, depression and spatial memory impairment induced by mild traumatic brain injury. Furthermore, we investigated whether these neurobehavioral or neurodegenerative complications can be lessened by administration of a novel putative neuroprotective peptide. Methods: Age-matched lean and fatty diabetic Zucker rats were tested in the sucrose preference test (anhedonia), open field test in bright light (anxiety measure) and the Morris water maze (spatial memory) prior to receiving a sham-injury or lateral fluid percussion (LFP) mild traumatic brain injury. Behavioral testing was repeated at 1-week, 1-month, and 3-month intervals following injury. A synthetic peptide consisting of a portion of the 5- hydroxytryptamine (serotonin) 2A receptor (2 mg/kg) (or vehicle) was administered via intraperitoneal route every other day for 7 days after sham or LFP injury to lean rats or 7 days before and after sham or LFP injury to fatty rats. Results: Sucrose preference decreased transiently (one week after mild traumatic brain injury) in Zucker lean rats indicative of anhedonia. Baseline anxiety-like behavior (bright light, open field test) was lower in fatty vs. lean Zucker rats, and anxiety behavior increased significantly in fatty rats but not lean rats following mild traumatic brain injury. Mild traumatic brain injury impaired recall of spatial memory in fatty and lean rats, and the effect was longer-lasting in fatty rats. A synthetic peptide fragment of the 5-hydroxytryptamine 2A receptor enhanced recall of spatial learning one-week after sham injury in Zucker rats and it may have prevented ‘anhedonia’ one-week after TBI (LFP) in a subset of Zucker fatty and lean rats expressing near-normal baseline sucrose preference. Mean plasma 5-hydroxytryptamine 2A receptor autoantibody level (determined 2 weeks after injury) was 2.5-fold higher than background, but did not differ significantly in (sham- vs TBI) Zucker lean rats. Conclusions: These are the first data to suggest reduced baseline anxiety-like behavior in Zucker fatty (vs. lean) rats. The pronounced increases in anxiety , and spatial memory impairment experienced by Zucker fatty (vs lean) rats following mild traumatic brain injury may have accounted in part for absence of a 5-hydroxytryptamine 2A receptor peptide neuroprotective effect in brain- injured Zucker fatty rats.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

Despite the available literature on traumatic brain injury (TBI) biomarkers elsewhere, data are limited or non-existent in sub-Saharan Africa (SSA). The aim of the study was to analyse associations in acute TBI between admission serum biomarker concentrations and TBI severity, CT-scan findings and outcome as well as explore the influence of concurrent Toxoplasma gondii infection. Concentrations of serum biomarkers (GFAP, NFL Tau, UCH-L1, and S100B) were measured and Toxoplasma gondii detected in samples obtained <24 hours post-injury. The GOSE was used to evaluate 6 months outcome. All biomarkers levels increased with severity of TBI, but this increase was significant only for NFL (P=0.01). GFAP values significantly increased (P=0.026) in those with unfavorable outcome. Tau levels were higher in those who died (P=0.017). GFAP and NFL were sensitive to CT-scan pathology (p values respectively 0.004 and 0.002). S100B levels were higher (P<0.001) in TBI patients seropositive to Toxoplasma gondii. NFL was found to be sensitive to TBI severity while NFL and GFAP were predictive of CT intracranial abnormalities. Increased levels of GFAP and Tau were associated with poorer outcomes 6 months after TBI. S100B levels were significantly higher in T. gondii seropositive TBI patients.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

Sports traumatic brain injury (TBI) accounts for up to 20% of all sports injuries, and the number of cases is growing year by year due to an increase in the number of people involved in sports, the growing popularity of extreme and contact sports, as well as a high level of motivation to achieve record results. Mild TBI dominates, which can provoke the development of a very wide range of complications and negative consequences. In the programs for the prevention of complications and the rehabilitation of athletes after TBI, TBI features are not sufficiently considered, which significantly differ from household, road or criminal injuries. There are no instrumental methods for diagnosing the severity of the injury. Sports TBI is characterized by repeated frequent TBI, elevated body and brain temperature, peripheral redistribution of blood flow and hypocapnia, which significantly affect cerebral blood flow. Brain injury is an independent cause of the development of cerebral hyperthermia, which significantly worsens the consequences of TBI. To diagnose sports TBI, the method of microwave radiometry of the brain (MWR) can be used. For the prevention of complications, the technology of craniocerebral hypothermia (CCH), which allows for to reduce of physical general and cerebral hyperthermia, and increases the resistance of cerebral cortex neurons to hypoxia and trauma could be used However, these approaches in sports medicine are used sporadically, which, is due to the lack of awareness of coaches and doctors of sports teams. The purpose of the review is to present MWR and CCH in sports TBI.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Rhodotorula mucilaginosa fungaemia is rare and highly resistance to antifungal therapy. We herein report a case involving a 31-year-old male admitted after a high-velocity road traffic accident. He sustained a grade IV liver injury with right hepatic vein thrombosis, necessitated an urgent laparotomy. Post-operatively, repeated imaging of the abdomen revealed presence of biloma. Percutaneous subdiaphragmatic drainage was done but appeared ineffective, prompting second surgery for a urgent hemi-hepatectomy. Patient then was nursed in the intensive care unit (ICU) however during his stay in the ICU he became more sepsis evident by worsening ventilatory support and rise in septic parameters from the biochemistry parameters. Despite on intravenous piperacillin-tazobactam and fluconazole, his septic parameters did not improve and a full septic workup was done and was found to be positive for Rhodotorula mucilaginosa from the blood cultures. After discussion with the infectious disease physicians and clinical microbiologist, it was decided to initiate a course of intravenous meropenem and amphotericin B based on minimum inhibitory concentration (MIC) values, considering the patient's extended ICU stay and catheter use. Eventually, successful weaning off mechanical ventilation was discharge from ICU care. This case underscores the necessity of individualized approaches, combining timely imaging, appropriate drainage techniques, and tailored treatments to optimize outcomes for such intricate post-traumatic complications.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Traumatic brain injury (TBI) affects millions of people annually, however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In the current study we used the central fluid percussion injury (CFPI) model in a micro pig to study the potential scalability of these diffuse pathologies in a gyrencephalic brain of a species with inflammatory systems very similar to humans. We found that both axonal injury and microglia activation within the thalamus and corpus callosum are positively correlated to the weight-normalized pressure pulse, while subtle changes in blood gas and mean arterial blood pressure are not. We also found that the majority of tissue generated up to 10 years previously is viable for immunofluorescent labeling after long-term refrigeration storage. This study indicates that a micro pig CFPI model could allow for specific investigations of various degree of diffuse pathological burdens following TBI.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

This prospective cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore the response of an early intensive neurorehabilitation protocol. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the structural and protective role of proteins and release of neurotrophic factors. Furthermore, parametrization of FES was according to presence or absence of deep pain. Results have shown 72.6% (16/22) cats that achieved ambulation, with 9 cats within 15 days, 2 cats until 30 days and 5 cats until 60 days, however with persistent knuckling position. During the 4 years follow-up, there was evidence of improvement on both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied at the first weeks after injury and accurate parametrization according to deep pain perception, may improve functionality and ambulation, reducing probability of amputation of the affected limb.

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore the response of an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal ap-proach were based on the potential structural and protective role of proteins and release of neurotrophic factors. Furthermore, parametrization of FES was according to the presence or absence of deep pain. Results have shown that 72.6% (16/22) cats achieved ambulation, with 9 cats within 15 days, 2 cats until 30 days and 5 cats until 60 days. During the 4 years follow-up, there was evidence of improvement on both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES ap-plied at the first weeks after injury and accurate parametrization according to the deep pain perception, is suggestive to help in functional recovery and ambulation, reducing probability of amputation.

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in the study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

Various therapeutic approaches have been developed for neglect. Many studies have demonstrated the effect of Digital therapeutics(DTx) on neglect. By contrast, only a few studies have reported on the effects of DTx on egocentric and allocentric neglect. In this article, seven studies on DTx of egocentric and allocentric neglect were reviewed. DTx, which was employed in these studies, could be classified as follows: 1) software adaptation in traditional treatment, 2) VR game using the head-mount display as treatment, and 3) development of new digital program like ReMoVES. In addition, more studies and effective results were reported on egocentric neglect than allocentric neglect. In future studies, each effect on egocentric and allocentric neglect should be identified in detail through the appropriate use of differential evaluation and long-term application of independent digital therapeutics.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach could not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies including electrical stimulation, training, pharmacological treatments, or cell implantation that resulted in improvements in locomotor behaviour, rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers to classify these populations.

. Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurological disability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads to insufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrial dysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemic brain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, a selective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whether raloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model. Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nM and 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygen-glucose deprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifene improved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.

Background: Early diagnosis of acute brain injury (ABI) is critical for patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. Methods: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and Tau were collected daily after VA-ECMO cannulation and measured using a multiplex platform. Primary outcomes were the occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). Results: Of 20 consented patients (median age=48.5 years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcomes at discharge. 10 (50%) patients were centrally cannulated. The median duration on ECMO was 4.5 days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. Conclusion: Plasma biomarkers may facilitate early detection of ABIs in VA-ECMO where neurological exam is limited and assist timely clinical decision-making.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

Trauma to the spinal cord causes extensive neuronal death contributing to the loss of sensory-motor and autonomic functions below the injury level. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise of caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesize that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mouse with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using the human SH-SY5Y cells overexpressing XIAP we show further that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome after spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

Here we performed a comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and copper content in the injured and uninjured areas of the frontal lobes and the hippocampus of the brain of male Wistar rats, after modeling of combined brain and spinal cord injury. Brain and spinal cord injury were modelled by local destruction of the left precentral region of the brain using a stylet followed by hemorrhage injury at the level of the first lumbar vertebra of the spinal cord. We found a significant decrease in NO production 7 days after injury modeling in the injured and uninjured (contralateral) brain regions, but the copper content remained unchanged one week after injury modeling. Thus, combined brain and spinal cord injury is not accompanied by a radical change in the activity of the antioxidant system in the brain, which is also confirmed by the absence of changes in NO production and copper content in the hippocampus.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

In recent years, advancements in brain science and neuroscience have significantly influenced the field of computer science, particularly in the domain of reinforcement learning (RL). Drawing insights from neurobiology and neuropsychology, researchers have leveraged these findings to develop novel mechanisms for understanding intelligent decision-making processes in the brain. Concurrently, the emergence of quantum computing has opened new frontiers in artificial intelligence, leading to the development of quantum machine learning (QML). This study introduces a novel model that integrates Quantum Spiking Neural Networks (QSNN) and Quantum Long Short-Term Memory (QLSTM) architectures, inspired by the complex workings of the human brain. Specifically designed for reinforcement learning tasks in energy-efficient environments, our approach progresses through two distinct stages mirroring sensory and memory systems. In the initial stage, analogous to the brain’s hypothalamus, low-level information is extracted to emulate sensory data processing patterns. Subsequently, resembling the hippocampus, this information is processed at a higher level, capturing and memorizing correlated patterns. We conduct a comparative analysis of our model against existing quantum models such as Quantum Neural Networks and their classical counterparts, elucidating its unique contributions. Through empirical results, we aim to underscore the effectiveness of our approach in optimizing energy consumption in practical scenarios.

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

People experiencing homelessness are at risk from a number of co-morbidities including traumatic brain injury, mental health disorders and various infections. Little is known about the rehabilitation needs of this population. This study took advantage of unique access to a specialist ‘Access’ GP practice for people experiencing homelessness and a local inclusion health initiative to explore the five year period prevalence of these conditions in a population of people experiencing homelessness, through electronic case record searches; and identify barriers and facilitators to healthcare provision for this population in the context of an interdisciplinary and multi specialist inclusion health team, through semi structured interviews with 12 staff working in primary and secondary care who interact with this population. The five year period prevalence of TBI, infections and mental health disorders was 9.5%, 4% and 22.8% respectively. Of those who had suffered a brain injury only 3, had accessed rehabilitation services. Themes from thematic analysis of interviews included: lack of resource, stigmatisation, under recognised multi-morbidity (including from brain injury) as barriers, trauma-informed, person-centred, adaptable, &amp; integrated and collaborative models of care as facilitators. The combination of quantitative and qualitative data suggests a potential role for rehabilitation medicine in inclusion health initiatives.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Previous studies suggested that trauma-focused cognitive behavior therapy (TF-CBT) is effective in reducing symptoms of post-traumatic stress disorder (PTSD) and depression in children and adolescents. However, the effects of app-assisted TF-CBT-based interventions in psychiatric clinics compared to treatment-as-usual (TAU) are under-explored. The purpose of this study was to reveal the added value of the app-assisted TF-CBT-based intervention as an add-on to TAU. The digitalized measures of the Child and Adolescent Trauma Screen (CATS), The Adolescent Dissociative Experience Scale (A-DES), Short Moods and Feelings Questionnaire (SMFQ), PTSD Checklist (PCL-5), and Children's Post-Traumatic Cognitions Inventory (CPTCI) were applied at baseline and post-treatment. The app-assisted TF-CBT-based group participants started with higher levels of negative alterations in cognition and mood compared to TAU participants but at post-treatment, no significant differences were observed between the app-assisted TF-CBT and TAU groups. Within the app-assisted TF-CBT group, post-treatment scores were significantly lower in post-traumatic stress symptoms, intrusion symptoms, alterations in arousal and reactivity, overall post-traumatic cognitions, and belief in being "a fragile person in a scary world”. Within the TAU group, post-treatment scores were notably lower just in dissociation and intrusion symptoms. The study suggests that app-assisted TF-CBT-based intervention can be effective in addressing specific trauma-related symptoms. The findings imply the necessity for screening for traumatic experiences, incorporating trauma-informed care, implementation of TF-CBT into treatment protocols, utilization of app-assisted interventions, tailoring interventions to individual needs, and comprehensive assessment and monitoring of treatment progress.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Sensory integration is an essential function of human life, and its decline causes difficulties in the quality of life, especially in older adults. In this study, we proposed an arm-reaching task based on a virtual reality head-mounted display (VR-HMD) system to assess sensory integration in daily life, and examined whether reaching task performance was associated with age and resting-state functional connectivity (rsFC) between the brain regions of interest involved in sensory integration. We hypothesized that performance during a reaching task with multiple cognitive loadings would be affected by aging. The gap angle between the reaching hand and target positions was compared between older and middle-aged adults as a measure of sensory integration function. In addition, rsFC, which was significantly correlated with the gap angles of individual participants in the older adult group, was identified using resting-state functional magnetic resonance imaging data. The mean gap angle was significantly larger in the older adults than in the middle-aged group and was also significantly correlated with connections between the left primary motor area and the left inferior temporal gyrus, temporo-occipital part. Because the connectivity between the areas is known to be related to visuomotor integration, the results suggest the involvement of visuomotor integration in the decline of sensory integration function in old age and the validity of the gap angle during the proposed VR-HMD task as an index for the decline in function.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P&lt;0.05), left hippocampus volume (LHV, β: -0.02435, P&lt;0.01) and right hippocampus volume (RHV, β: -0.02544, P&lt;0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P&lt;0.05) and LHV (β: -0.01173, P&lt;0.05) and RHV (β: -0.01193, P&lt;0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P&lt;0.05; RHV, β: -0.005527, P&lt;0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

The advent of deep learning (DL) has revolutionized medical imaging, offering unprecedented avenues for accurate disease classification and diagnosis. DL models have shown remarkable promise for classifying brain tumor from Magnetic Resonance Imaging (MRI) scans. However, despite their impressive performance, the opaque nature of DL models poses challenges in understanding their decision-making processes, particularly crucial in medical contexts where interpretability is essential. This paper explores the intersection of medical image analysis and DL interpretability, aiming to elucidate the decision-making rationale of DL models in brain tumor classification. Leveraging state-of-the-art DL frameworks with transfer learning, we conduct a comprehensive evaluation encompassing both classification accuracy and interpretability. Using state-of-the-art DL frameworks with transfer learning, we conduct a thorough evaluation covering both classification accuracy and interpretability. We employ adaptive path-based techniques to understand the underlying decision-making mechanisms of these models. Grad-CAM and Grad-CAM++ highlight critical image regions where the tumors are located.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

Modularity is arguably one of the most influential theses guiding research on brain and cognitive function since phrenology. This paper considers the following question: is modularity entailed by recent Bayesian models of brain and cognitive function, especially the predictive processing framework? It starts by considering three of the most well-articulated arguments for the view that modularity and predictive processing work well together. It argues that all three kinds of arguments for modularity come up short, albeit for different reasons. The analysis in this paper, although formulated in the context of predictive processing, speaks to broader issues with how to understand the relationship between functional segregation and integration and the reciprocal architecture of the predictive brain. These conclusions have implications for how to study brain and cognitive function. Specifically, when cognitive neuroscience works within an acyclic Markov decision scheme, adopted by most Bayesian models of brain and cognitive function, it may very well be methodologically misguided. This speaks to an increasing tendency within the cognitive neurosciences to emphasise recurrent and reciprocal neuronal processing captured within newly emerging dynamical causal modelling frameworks. The conclusions also suggest that functional integration is an organising principle of brain and cognitive function.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

Traumatic pneumothorax (PTX) occurs in up to 50% of patients with severe polytrauma and chest injuries. Patients with traumatic PTX with clinical signs of tension physiology and hemodynamic instability are typically treated with an urgent decompressive thoracostomy, tube thoracostomy, or needle decompression. There is recent evidence that non-breathless patients with hemodynamically stable traumatic PTX can be managed conservatively through observation or a percutaneous pigtail catheter. We present here a 52-year-old woman who presented to the emergency department with 55 mm traumatic PTX. Following aspiration of 1500 ml of air, clinical improvement was immediately observed, allowing the patient to be discharged shortly thereafter. In hemodynamically stable patients with posttraumatic PTX, without specific risk factors or oxygen desaturation, observation or simple needle aspiration can be a reasonable approach. We aimed in this article to review the available literature on needle aspiration and conservative treatment of traumatic pneumothorax. A total of 12 studies were selected out of 190 articles on traumatic PTX, where conservative treatment versus chest tube decompression was compared. Our case report demonstrated that even a large PTX in a hemodynamically stable patient without other risk conditions, can be successfully treated conservatively with simple needle aspiration to avoid tube thoracostomy complications.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES) were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE¹. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of a SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

Orbital fractures are a common finding in facial trauma and serious complications may arise when orbital reconstruction is not done properly. The virtual planning can be used to manufacture patient-specific titanium orbital implants (PSI) through the process of selective laser melting. This method is currently considered the most accurate technique for orbital reconstruction. Even with the most accurate tehniques of bone reconstruction, there are still situations where enophthalmos is present after reconstruction which may be produced by intraorbital soft tissue atrophy. The aim of this paper was to evaluate the orbital soft tissue after postraumatic reconstruction of the orbital walls fractures. 10 patients diagnosed with unilateral orbital fractures were included in this study. A CT scan of the head region with thin slices (0.6mm) and soft and bone tissue windows was done. After data processing, the STL files were exported and the intraorbital fat tissue volume and the muscular tissue volume were masured. The volumes of affected orbit tissues were compared with the volumes of the healthy orbit tissues for each patient. Our findings conclude that a higher or a lower grade of fat and muscular tissue loss is present in all cases of reconstructed orbital fractures.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 &amp; 0.91, p values = 0.001, 95% CI: 0.80-0.92 &amp; 0.87 to 0.94, sensitivity = 0.85 &amp; 0.87, specificity = 0.73 &amp; 0.83, Youden index = 0.58 &amp; 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.

Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to OA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible). Right knee joints of the mice were injured using a non-invasive tibial compression injury model that closely mimics ACL rupture in humans and global gene expression was quantified before and at 1-day, 1-week, and 2-weeks post-injury using RNA-seq. Following injury, STR/ort displayed severe cartilage degeneration while MRL/MpJ had little cartilage damage. Gene expression analysis suggested that prolonged inflammation and elevated catabolic activity in STR/ort injured joints, compared to the other two strains may be responsible for the severe PTOA phenotype observed in this strain. MRL/MpJ had the lowest expression values for several inflammatory cytokines and catabolic enzymes activated in response to ACL injury. Furthermore, we identified several genes highly expressed in MRL/MpJ compared to the other two strains including B4galnt2 and Tpsab1 which may contribute to enhanced healing in the MRL/MpJ. Overall, this study has increased our knowledge of early molecular changes associated with PTOA development.

Background: Post-traumatic stress disorder (PTSD) is a mental health concern among traumatized children and adolescents. The specific objective is to describe post-traumatic stress disorder in children (6 to 12 years old) and adolescents (12 to 18 years old). This comprehensive review compiles the clinical interventions targeting PTSD in this age group and systematizes the empirical evidence about their efficacy. Methods: The PRISMA method was used to present and evaluate the clinical interventions implemented for PTSD. Results: Significant symptoms of PTSD include avoidance, overstimulation, and flashbacks, typically accompanied by a depressed mood and anxiety. Cognitive Behavioral Therapy (CBT), trauma-focused CBT, Eye Movement Desensitization and Reprocessing (EMDR), Systemic Therapy, Play Therapy, Exposure Therapy, Relaxation Techniques, and Psychodynamic Psychotherapy are essential interventions for the treatment of patients between the ages of 6 and 18. CBT, particularly Trauma-focused CBT, is the most effective and extensively used therapy for dealing with cases of juvenile PTSD, according to the findings of the vast majority of previous research. Conclusions: The present systematic review summarizes the findings of several studies on psychotherapeutic interventions for PTSD in children and adolescents. PTSD in this population differs from PTSD in adults, necessitating various age-appropriate approaches and therapeutic models.

Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players including 46 professional, 98 semi-professional and 145 amateur players were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT genotype of the GDF5 gene, TT and CT genotypes of AMPD1 gene, TT genotype of COL5A1 and GG genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined response (R) process that is generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external interactions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight or run, while glucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecond-scale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. The prevalence of PTSD is estimated to be 5-10% worldwide, and it is associated with significant distress and disability. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer’s dementia and Parkinson’s disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. In the current review, the PubMed and Scopus databases were searched for studies aimed at identifying genetic, biochemical, neuroimaging or behavioral markers associated with neurodegeneration in patients with PTSD. Out of a total of 342 citations retrieved, 29 relevant studies were identified for inclusion in the review. The results of these studies suggest that several potentially relevant biological markers, including cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome and parasomnias, may be associated with an increased risk of neurodegeneration in patients with PTSD. Though many of these results need replication, they highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders, and suggest potentially valuable avenues for prevention and early intervention in this patient population.

The main purpose of this article is to identify brain diseases such as Alzheimer's and Parkinson's in an intelligent way using Python software and processing the function of neurons in the neural network areas of the brain, which are classified into different components, and the data is based on the information obtained from FMRI images using algorithms artificial intelligence can intelligently diagnose the type of disease. Therefore, by using spatial clustering based on the deep learning method with noise algorithm (DBSCAN), fMRI brain image and fMRI brain surface complexity are classified, and then image preprocessing will be applied to fMRI images by using artificial intelligence neural networks (ANN) algorithm. became. Then, by using the ANN algorithm and Deep CNN topology of the brain neural network, the type of disease in the brain can be diagnosed by simulating the performance of an artificial neural network (ANN) in Python software. Deep machine learning-based methods, especially algorithms based on neural networks, have shown great success in medical image analysis for various tasks including brain tumor detection, segmentation, and classification, and Alzheimer's and epilepsy. In this research, we propose an integrated model based on a convolutional neural network for simultaneous recognition and classification of brain diseases for intelligent diagnosis of tumors and epilepsy. The average accuracy obtained from our proposed model is 97.89 percent accuracy and 91.66 percent specificity.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.