Treatment Of Traumatic Brain Injury Research Articles

Cisternostomy associated with decompressive craniectomy for traumatic brain injury: a systematic review and meta-analysis.

Decompressive craniectomy (DC) has been the main surgical treatment of refractory high intracranial pressure (ICP) in traumatic brain injury (TBI) for decades. Basal cisternostomy emerged as a novel option in brain trauma, with results still unclear. We performed a systematic review and meta-analysis comparing cisternostomy added to conventional DC versus DC alone for the treatment of TBI. This study was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Three databases were systematically searched for studies comparing cisternostomy + DC versus DC alone. Primary outcomes were overall mortality, length of stay in ICU care, duration of mechanical ventilation. Review Manager was used for statistical analysis and I2 measured heterogeneity. A total of seven studies and 980 patients were included in this meta-analysis, 473 in the cisternostomy + DC group and 507 in the DC group. Age ranged from 14 to 69 years old, with 76% male patients. Overall mortality was significantly lower in the cisternostomy + DC group (OR 0.70; 95% CI 0.53-0.92; p = 0.01; I2 = 31%). Length of stay in ICU care was significantly reduced in the patients submitted to cisternostomy + DC (OR -4.58; CI -6.78, -2.37); p < 0.0001; I2 = 35%). The mean duration in mechanical ventilation was significantly lower in the group submitted to cisternostomy + DC (-3.49; 95% CI-6.79, -0.20; p = 0.04; I2 = 86%). Regarding functional outcomes, the scarce and heterogeneous data were not sufficient to make any conclusion about the effect of cisternostomy on functional outcomes, but tends to favor patients who underwent cisternostomy combined with DC. In this meta-analysis, the implementation of cisternostomy added to conventional DC was associated with lower mortality, days in mechanical ventilation and length of stay in ICU care. Larger prospective and randomized cohorts are necessary to recommend this procedure on a large scale.

Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury.

Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%. While there are several potential explanations for this, previous clinical trials have relied on extrapolation from preclinical studies for critical design considerations, including drug dose optimization, post-injury drug treatment initiation and duration. Incorporating clinically relevant biomarkers in preclinical studies may provide an opportunity to calibrate preclinical models to identical (or similar) measurements in humans, link to human TBI biomechanics and pathophysiology, and guide therapeutic decisions. To support this translational goal, we conducted a systematic literature review of preclinical TBI studies in rodents measuring blood levels of clinically used GFAP, UCH-L1, NfL, t-Tau, or p-Tau, published in PubMed/EMBASE up to April 10th, 2024. Although many factors influence clinical TBI outcomes, many of those cannot routinely be assessed in rodent studies (e.g., ICP monitoring), thus we focused on blood biomarkers' temporal trajectories and discuss our findings in the context of the latest clinical TBI biomarker data. Out of the 805 original preclinical studies, 74 met the inclusion criteria, with a median quality score of 5 (25th-75th percentiles: 4-7) on the CAMARADES checklist. GFAP was measured in 43 studies, UCH-L1 in 21, NfL in 20, t-Tau in 19, and p-Tau in seven. Data in rodent models indicate that all biomarkers exhibited injury severity-dependent elevations with distinct temporal profiles. GFAP and UCH-L1 peaked within the first day after TBI (30- and 4-fold increases, respectively, in moderate-to-severe TBI versus sham) with the highest levels observed in the contusion TBI model. NfL peaked within days (18-fold increase) and remained elevated up to 6 months post-injury. GFAP and NfL show a pharmacodynamic response in 64.7% and 60%, respectively, of studies evaluating neuroprotective therapies in preclinical models. However, GFAP's rapid decline post-injury may limit its utility for understanding the response to new therapeutics beyond the hyperacute phase after experimental TBI. Furthermore, as in humans, subacute NfL levels inform on chronic white matter loss after TBI. t-Tau and p-Tau levels increased over weeks after TBI (up to 6- and 16-fold, respectively); however, their relationship with underlying neurodegeneration has yet to be addressed. Further investigation into biomarker levels in the subacute and chronic phases after TBI will be needed to fully understand the pathomechanisms underpinning blood biomarkers' trajectories and select the most suitable experimental model to optimally relate preclinical mechanistic studies to clinical observations in humans. This new approach could accelerate the translation of neuroprotective treatments from laboratory experiments to real-world clinical practices.

Antisecretory Factor 16 (AF16): A Promising Avenue for the Treatment of Traumatic Brain Injury—An In Vitro Model Approach

Traumatic brain injury (TBI) is caused by an external mechanical force to the head, resulting in abnormal brain functioning and clinical manifestations. Antisecretory factor (AF16) is a potential therapeutic agent for TBI treatment due to its ability to inhibit fluid secretion and decrease inflammation, intracranial pressure, and interstitial fluid build-up, key hallmarks presented in TBI. Here, we investigated the effect of AF16 in an in vitro model of neuronal injury, as well as its impact on key components of the autophagy pathway and mitochondrial dynamics. N2Awt cells were treated with AF16, injured using a scratch assay, and analysed using confocal microscopy, correlative light and electron microscopy (CLEM), flow cytometry, and western blotting. Our results reveal that AF16 enhances autophagy activity, regulates mitochondrial dynamics, and provides protection as early as 6 h post-injury. Fluorescently labelled AF16 was observed to localise to lysosomes and the autophagy compartment, suggesting a role for autophagy and mitochondrial quality control in conferring AF16-associated neuronal protection. This study concludes that AF16 has potential as a therapeutic agent for TBI treatment through is regulation of autophagy and mitochondrial dynamics.

Bioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury

Traumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. In vitro experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in H2O2 environment, regulate RAW264.7 polarization from M1 to M2 phenotype and promote HUVEC angiogenesis. In vivo experiments demonstrated that GC/I/E hydrogel reduced brain oedema and Nissl body damage, inhibited inflammatory expression of G3-FFAP and neural scarring, improved microvascular and vascular function reconstruction, and facilitated neuronal and synaptogenesis, ultimately improving neurofunctional recovery in TBI. RNA sequencing results demonstrated that GC/I/E hydrogel treatment significantly correlated with the regulation of genes such as apoptosis, inflammation regulation, and neural regeneration. This bioactive hydrogel with neuroprotection, inflammation modulation and promotion of angiogenesis has great potential for TBI treatment.

Implantation of MSC spheroid-derived 3D decellularized ECM enriched with the MSC secretome ameliorates traumatic brain injury and promotes brain repair

Traumatic brain injury (TBI) presents substantial clinical challenges, as existing treatments are unable to reverse damage or effectively promote brain tissue regeneration. Although implantable biomaterials have been proposed to support tissue repair by mitigating the adverse microenvironment in injured brains, many fail to replicate the complex composition and architecture of the native extracellular matrix (ECM), resulting in only limited therapeutic outcomes. This study introduces an innovative approach by developing a mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) decellularized ECM (dECM) that is enriched with the MSC-derived matrisome and secretome, offering a promising solution for TBI treatment and brain tissue regeneration. Proteomic and cytokine array analyses revealed that 3D dECM retained a diverse array of MSC spheroid-derived matrisome proteins and secretome components, which are crucial for replicating the complexity of native ECM and the therapeutic capabilities of MSCs. These molecules were found to underlie the observed effects of 3D dECM on immunomodulation, proneuritogenesis, and proangiogenesis in our in vitro functional assays. Implantation of 3D dECM into TBI model mice effectively mitigated postinjury tissue damage and promoted brain repair, as evidenced by a reduced brain lesion volume, decreased cell apoptosis, alleviated neuroinflammation, reduced glial scar formation, and increased of neuroblast recruitment to the lesion site. These outcomes culminated in improved motor function recovery in animals, highlighting the multifaceted therapeutic potential of 3D dECM for TBI. In summary, our study elucidates the transformative potential of MSC spheroid-derived bioactive 3D dECM as an implantable biomaterial for effectively mitigating post-TBI neurological damage, paving the way for its broader therapeutic application.

Traumatic brain injury rehabilitation for warfighters with post-traumatic stress.

While there is extensive empirical support and clinical guidance for the treatment of mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) individually, less is known about treating the comorbid presentation of both conditions. The purpose of this review article is to provide information on the mental health treatment needs of service members (SMs) engaged in traumatic brain injury (TBI) rehabilitation. It also aims to offer a framework for an integrated treatment approach to address the cognitive and psychological health needs of warfighters. We review the prevalence and outcomes associated with comorbid TBI and PTSD and present relevant access to care considerations. Additionally, we identify an integrated approach to TBI treatment which takes psychological trauma into consideration. We introduce a trauma-informed care (TIC) model with specified diagnostic and treatment considerations for the service member and veteran (SM/V) communities. TIC is a strengths-based framework that raises the system-wide awareness of treatment facilities to the impact of psychological trauma on behavioral health. A comprehensive diagnostic approach is recommended with considerations for symptom etiology. Clinical considerations derived from available guidelines are identified to meet critical treatment needs for SM/Vs presenting for TBI treatment with a remote history of mTBI and psychological trauma or known PTSD. Clinical practice guidelines are used to inform an integrated TBI treatment model and maximize rehabilitation efforts for warfighters. Given the prevalence of comorbid TBI and PTSD among SM/Vs and its impact on outcomes, this review presents the integration of appropriate diagnostics and treatment practices, including the incorporation of CPGs into TBI rehabilitation.

One-year follow-up of neurobehavioral therapy in functional seizures or epilepsy with traumatic brain injury: A nonrandomized controlled trial.

Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy. In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life. Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-onlycomparisons improved on only one of 19 (5.3%). NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures.

Vinpocetine Ameliorates Neuronal Injury After Cold-Induced Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), also known as intracranial injury, is a common condition with the highest incidence rate among neurodegenerative disorders and poses a significant public health burden. Various methods are used in the treatment of TBI, but the effects of cold-induced traumatic brain injury have not been thoroughly studied. In this context, vinpocetine (VPN), derived from Vinca minor, exhibits notable anti-inflammatory and antioxidant properties. VPN is known for its neuroprotective role and is generally utilized for treating various neurodegenerative disorders. However, the function of VPN after cold-induced TBI needs to be studied in more detail. This study aims to investigate the neuroprotective effects of VPN at varying doses (5mg/kg or 10mg/kg) after cold-induced TBI. C57BL/6 mice were sacrificed 2 or 28days after cold-induced TBI. Results indicate that VPN administration significantly reduces brain infarct volume, brain swelling, blood-brain barrier disruption, and DNA fragmentation in a dose-dependent manner. Additionally, VPN enhances neuronal survival in the ipsilesional cortex. In the long term, VPN treatment (5mg/kg/day or 10mg/kg/day, initiated 48h post-TBI) improved locomotor activity, cell proliferation, neurogenesis, and decreased whole brain atrophy, specifically motor cortex atrophy. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the underlying mechanisms to profile proteins and signaling pathways influenced by prolonged VPN treatment post-TBI. Notably, we found that 192 different proteins were significantly altered by VPN treatment, which is a matter of further investigation for the development of therapeutic targets. Our study has shown that VPN may have a neuroprotective role in cold-induced TBI.

Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global health issue that affects millions of people every year. It is caused by any form of external force, resulting in temporary or permanent impairments in the brain. The pathophysiological process following TBI usually involves excitotoxicity, mitochondrial dysfunction, oxidative stress, inflammation, ischemia, and apoptotic cell death. It is challenging to find treatment for TBI due to its heterogeneous nature, and no therapeutic interventions have been approved thus far. Neurotrophins may represent an alternative approach for TBI treatment because they influence various functional activities in the brain. The present review highlights recent studies on neurotrophins shown to possess neuroprotective roles in TBI. Neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have demonstrated reduced neuronal death, alleviated neuroinflammatory responses and improved neurological functions following TBI via their immunomodulatory, anti-inflammatory and antioxidant properties. Further studies are required to ensure the efficacy and safety of neurotrophins to be used as TBI treatment in clinical settings.

Bibliometric analysis of traumatic brain injury in the neurosciences field from the past 10 years

Traumatic brain injury (TBI) is a common neurological disorder that causes severe problems in lack of effective treatment. This study aims to investigate the burgeoning trends of TBI in the field of neurosciences and offer insights for future research. Web of Science (WOS) was used to download data of TBI. The topic of “traumatic brain injury” in the neurosciences research area has been investigated during the period 2015–2024 and the research trends through VOSviewer, Pajek, and Excel software. According to the retrieval, 2476 articles in journals with an impact factor of 5 or higher were exported. The United States of America (USA) is the most productive, followed by China, Canada, England, and Australia. The top five organizations in terms of publication count include the University of Pennsylvania, the University of Pittsburgh, Harvard Medical School, Uniformed Services University of the Health Sciences, and the University of Melbourne. The journal, Neural Regeneration Research, is the most productive. Shultz, Sandy R. publishes the highest number of articles. Keyword cluster analysis shows that currently researchers’ studies mainly focus on TBI, followed by inflammation, neuroinflammation, Alzheimers-disease, and neuroprotection. This review offers a comprehensive summary and analysis of TBI in the neurosciences area. In the last 10 years, the number of high‐quality papers in this field has increased significantly, and increasing treatments for TBI have been provided.

Loss of microglial Arid1a exacerbates microglial scar formation via elevated CCL5 after traumatic brain injury

Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI.

Metabolomics integrated with network pharmacology of blood-entry constituents reveals the bioactive component of Xuefu Zhuyu decoction and its angiogenic effects in treating traumatic brain injury

BackgroundXuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated.ObjectivesThis study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI.MethodsThe study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments.ResultsMetabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002.ConclusionBy applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Increased incidence of weight-loss-associated humane endpoints in rats administered buprenorphine slow-release LAB formulation following traumatic brain injury: a retrospective study.

Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study's unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations' effects on laboratory animals.

The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. We show that neurons that activate ATF3 upregulate stress-related genes while repressing many genes, including commonly used markers for these cell types. Using an inducible reporter linked to ATF3, we genetically mark damaged cells to track them over time. Notably, we find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and retains the ability to fire action potentials. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive kinase MAP3K12, also known as dual leucine zipper kinase (DLK), is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our novel approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts.

Identification and Validation of Endoplasmic Reticulum Stress-Related Gene in Traumatic Brain Injury.

Endoplasmic reticulum stress (ERS) plays an essential role in the development of traumatic brain injury (TBI). We aimed to identify and validate the potential ERS-related genes of TBI through bioinformatics analysis and in vitro cell experiment. A total of 19 TBI and ERS-related genes were obtained from the GeneCards database and Comparative Toxicogenomics Database (CTD). Enrichment analysis primarily enriched in apoptosis. NFE2L2 was identified as a hub gene based on the protein-protein interactions (PPI) network that combined seven ranked methods included in cytoHubba. To further explore the effect of Nrf2, the protein encoded by NFE2L2, on ERS-induced apoptosis, we conducted cell experiments with tert-butylhydroquinone (tBHQ), the classical inducer of Nrf2. Western blot suggested tBHQ pretreatment could diminish ERS and reduce the protein expressions of apoptosis in the primary cultured neuron injury model. These data may establish some theoretical basis for the treatment of TBI and provide inspiration and innovative ideas for clinicians and pathologists to understand TBI comprehensively.

The application of mesenchymal stem cells in the treatment of traumatic brain injury: Mechanisms, results, and problems.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be derived from a wide variety of human tissues and organs. They can differentiate into a variety of cell types, including osteoblasts, adipocytes, and chondrocytes, and thus show great potential in regenerative medicine. Traumatic brain injury (TBI) is an organic injury to brain tissue with a high rate of disability and death caused by an external impact or concussive force acting directly or indirectly on the head. The current treatment of TBI mainly includes symptomatic, pharmacological, and rehabilitation treatment. Although some efficacy has been achieved, the definitive recovery effect on neural tissue is still limited. Recent studies have shown that MSC therapies are more effective than traditional treatment strategies due to their strong multi-directional differentiation potential, self-renewal capacity, and low immunogenicity and homing properties, thus MSCs are considered to play an important role and are an ideal cell for the treatment of injurious diseases, including TBI. In this paper, we systematically reviewed the role and mechanisms of MSCs and MSC-derived exosomes in the treatment of TBI, thereby providing new insights into the clinical applications of MSCs and MSC-derived exosomes in the treatment of central nervous system disorders.

The role of supplementation in traumatic brain injury among athletes and non-athletes population

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and long-term disability. The consequences following TBI can be persistent and cause life-long implications for survivors. Treatment of TBI may be complex and involve large monetary costs. The frequent injury mechanisms are traffic-related, falls, violence or sport-related accidents. Higher risk of brain injury and its complications indicate that people affected by brain trauma may benefit from the prophylactic and post-traumatic use of certain supplements both in the context of physical performance and in the event of potential injury. Aim of the Study: This narrative review examines the current literature of the role of supplementation before and after TBI and its effects on the patient's outcome. Materials and Methods: A comprehensive search was performed using PubMed and Google Scholar focusing on the literature published up to April 2024. The review included randomized controlled trials, meta-analyses, systematic reviews that focused on the use of creatine monohydrate, omega-3 fatty acids, magnesium and zinc in TBI and among the general population. Data of pathophysiology and epidemiology of TBI and safety profile of supplements were involved. Results: The evidence indicates that the role of supplementation with creatine, omega-3 PUFAs and zinc is important in mitigating secondary damage after TBI, as well as in protecting against damage if administered before injury. Conclusion: Because of the complex and multifactorial nature of the TBI more studies are required to constitute an effective nutrition-based strategy for reducing the cognitive and behavioral deficits associated with this injury. The evidence supporting multiple dietary components to improve a patient's outcome seems strong and the cost of its implementation is low. A group of particular interest that may benefit additionally are athletes who use dietary supplementation in their daily routine.

Exosomal miRNA-21 derived from umbilical cord mesenchymal stem cells inhibits microglial overactivation to counteract nerve damage.

Traumatic brain injury (TBI) is a major cause of neurological disability, and current treatments have limited effectiveness. Recent studies have emphasized the potential of exosomes derived from umbilical cord mesenchymal stem cells (UC-MSCs-Exo) in TBI treatment, but the molecular mechanisms underlying their therapeutic effects are not fully understood. In this study, UC-MSCs-Exo was isolated using ultracentrifugation and intraventricularly injected to TBI rat model. The neurofunctional motor function of the rats was evaluated using the modified neurological severity score (mNSS), and the activation of microglia was assessed through immunofluorescence detection of IBA1 expression levels. Additionally, we established an in vitro neuroinflammatory model using BV2 microglia to investigate the effects of UC-MSCs-Exo and miRNA-21. Our findings indicate that UC-MSCs-Exo promote neurological recovery in TBI rats and inhibit excessive microglia activation. Furthermore, UC-MSCs-Exo highly expresses miRNA-21 and inhibited the proliferation, migration, and release of inflammatory mediators of BV2 microglia by transporting miRNA-21. The present study suggests that the promotion of neurological recovery in TBI rats by UC-MSCs-Exo may be attributed to the inhibition of excessive microglia activation through miRNA-21.

Exploring the biological basis of acupuncture treatment for traumatic brain injury: a review of evidence from animal models.

Traumatic brain injury (TBI) occurs when external physical forces impact the brain, potentially causing long-term issues such as post-traumatic stress disorders and cognitive and physical dysfunctions. The diverse nature of TBI pathology and treatment has led to a rapid acceleration in research on its biological mechanisms over the past decade. This surge presents challenges in assessing, managing, and predicting outcomes for TBI cases. Despite the development and testing of various therapeutic strategies aimed at mitigating neurological decline after TBI, a definitive cure for these conditions remains elusive. Recently, a growing focus has been on preclinical research investigating acupuncture as a potential treatment method for TBI sequelae. Acupuncture, being a cost-effective non-pharmacological therapy, has demonstrated promise in improving functional outcomes after brain injury. However, the precise mechanisms underlying the anticipated improvements induced by acupuncture remain poorly understood. In this study, we examined current evidence from animal studies regarding acupuncture's efficacy in improving functional outcomes post-TBI. We also proposed potential biological mechanisms, such as glial cells (microglia astrocytes), autophagy, and apoptosis. This information will deepen our understanding of the underlying mechanisms through which acupuncture exerts its most beneficial effects post-TBI, assisting in forming new clinical strategies to maximize benefits for these patients.

Traumatic brain injury and sleep in military and veteran populations: A literature review.

Traumatic brain injury (TBI) is a hallmark of wartime injury and is related to numerous sleep wake disorders (SWD), which persist long term in veterans. Current knowledge gaps in pathophysiology have hindered advances in diagnosis and treatment. We reviewed TBI SWD pathophysiology, comorbidities, diagnosis and treatment that have emerged over the past two decades. We conducted a literature review of English language publications evaluating sleep disorders (obstructive sleep apnea, insomnia, hypersomnia, parasomnias, restless legs syndrome and periodic limb movement disorder) and TBI published since 2000. We excluded studies that were not specifically evaluating TBI populations. Highlighted areas of interest and knowledge gaps were identified in TBI pathophysiology and mechanisms of sleep disruption, a comparison of TBI SWD and post-traumatic stress disorder SWD. The role of TBI and glymphatic biomarkers and management strategies for TBI SWD will also be discussed. Our understanding of the pathophysiologic underpinnings of TBI and sleep health, particularly at the basic science level, is limited. Developing an understanding of biomarkers, neuroimaging, and mixed-methods research in comorbid TBI SWD holds the greatest promise to advance our ability to diagnose and monitor response to therapy in this vulnerable population.