Traumatic Brain Injuries: Manifestations, Evaluation, Management, and Outcomes.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03667. Author affiliations are listed at the end of this article.

Prevalence and Correlates of VA-Purchased Community Care Use Among Post-9/11-Era Veterans With Traumatic Brain Injury.

OBJECTIVE: Post-9/11-era veterans with traumatic brain injury (TBI) have greater health-related complexity than veterans overall, and may require coordinated care from TBI specialists such as those within the Department of Veterans Affairs (VA) healthcare system. With passage of the Choice and MISSION Acts, more veterans are using VA-purchased care delivered by community providers who may lack TBI training. We explored prevalence and correlates of VA-purchased care use among post-9/11 veterans with TBI. SETTING: Nationwide VA-purchased care from 2016 through 2019. PARTICIPANTS: Post-9/11-era veterans with clinician-confirmed TBI based on VA's Comprehensive TBI Evaluation (N = 65 144). DESIGN: This was a retrospective, observational study. MAIN MEASURES: Proportions of veterans who used VA-purchased care and both VA-purchased and VA-delivered outpatient care, overall and by study year. We employed multivariable logistic regression to assess associations between veterans' sociodemographic, military history, and clinical characteristics and their likelihood of using VA-purchased care from 2016 through 2019. RESULTS: Overall, 51% of veterans with TBI used VA-purchased care during the study period. Nearly all who used VA-purchased care (99%) also used VA-delivered outpatient care. Veterans' sociodemographic, military, and clinical characteristics were associated with their likelihood of using VA-purchased care. Notably, in adjusted analyses, veterans with moderate/severe TBI (vs mild), those with higher health risk scores, and those diagnosed with posttraumatic stress disorder, depression, anxiety, substance use disorders, or pain-related conditions had increased odds of using VA-purchased care. Additionally, those flagged as high risk for suicide also had higher odds of VA-purchased care use. CONCLUSIONS: Veterans with TBI with greater health-related complexity were more likely to use VA-purchased care than their less complex counterparts. The risks of potential care fragmentation across providers versus the benefits of increased access to care are unknown. Research is needed to examine health and functional outcomes among these veterans.

Epidemiological Burden of Neurotrauma in Nigeria: A Systematic Review and Pooled Analysis of 45,763 Patients.

OBJECTIVE: Neurotrauma is a significant cause of morbidity and mortality in Nigeria. We conducted this systematic review to generate nationally generalizable reference data for the country. METHODS: Four research databases and gray literature sources were electronically searched. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions and Cochrane's risk of bias tools. Descriptive analysis, narrative synthesis, and statistical analysis (via paired t-tests and χ2 independence tests) were performed on relevant article metrics (α = 0.05). RESULTS: We identified a cohort of 45,763 patients from 254 articles. The overall risk of bias was moderate to high. Most articles employed retrospective cohort study designs (37.4%) and were published during the last 2 decades (81.89%). The cohort's average age was 32.5 years (standard deviation, 20.2) with a gender split of ∼3 males per female. Almost 90% of subjects were diagnosed with traumatic brain injury, with road traffic accidents (68.6%) being the greatest cause. Altered consciousness (48.4%) was the most commonly reported clinical feature. Computed tomography (53.5%) was the most commonly used imaging modality, with skull (25.7%) and vertebral fracture (14.1%) being the most common radiological findings for traumatic brain injury and traumatic spinal injury, respectively. Two-thirds of patients were treated nonoperatively. Outcomes were favorable in 63.7% of traumatic brain injury patients, but in only 20.9% of traumatic spinal injury patients. Pressure sores, infection, and motor deficits were the most commonly reported complications in the latter. CONCLUSIONS: This systematic review and pooled analysis demonstrate the significant burden of neurotrauma across Nigeria.

Transcranial direct current stimulation promotes angiogenesis and improves neurological function via the OXA-TF-AKT/ERK signaling pathway in traumatic brain injury.

Traumatic brain injury (TBI) and its resulting complications pose a major challenge to global public health, resulting in increased rates of disability and mortality. Cerebrovascular dysfunction is nearly universal in TBI cases and is closely associated with secondary injury after TBI. Transcranial direct current stimulation (tDCS) shows great potential in the treatment of TBI; however, the exact mechanism remains elusive. In this study, we performed in vivo and in vitro experiments to explore the effects and mechanisms of tDCS in a controlled cortical impact (CCI) rat model simulating TBI. In vivo experiments show that tDCS can effectively reduce brain tissue damage, cerebral edema and neurological deficits. The potential mechanism may be that tDCS improves the neurological function of rats by increasing orexin A (OXA) secretion, upregulating the TF-AKT/ERK signaling pathway, and promoting angiogenesis at the injury site. Cellular experiments showed that OXA promoted HUVEC migration and angiogenesis, and these effects were counteracted by the ERK1/2 inhibitor LY3214996. The results of Matrigel experiment in vivo showed that TNF-a significantly reduced the ability of HUVEC to form blood vessels, but OXA could rescue the effect of TNF-a on the ability of HUVEC to form blood vessels. However, LY3214996 could inhibit the therapeutic effect of OXA. In summary, our preliminary study demonstrates that tDCS can induce angiogenesis through the OXA-TF-AKT/ERK signaling pathway, thereby improving neurological function in rats with TBI.

KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury.

Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the brain and which strategies most potently mitigate these processes. We developed a high-intensity ultrasound platform to inflict mechanical injury to induced pluripotent stem cell (iPSC)-derived cortical organoids. Mechanically injured organoids elicit classic hallmarks of TBI, including neuronal death, tau phosphorylation, and TDP-43 nuclear egress. We found that deep-layer neurons were particularly vulnerable to injury and that TDP-43 proteinopathy promotes cell death. Injured organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference screening, we identified a mechanosensory channel, KCNJ2, whose inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72 ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuronal death after brain injury, and we present a scalable, genetically flexible cerebral organoid model that may enable the identification of additional modifiers of mechanical stress.

[Injury mechanism, clinical status and prospects of traumatic brain injury].

Traumatic brain injury (TBI) is an important in the world's public health and an important subject of basic and clinical research in the medical field. In the past 30 years, the epidemiology, injury mechanism, safety prevention, medical strategies, nursing measures and other aspects of TBI have made great progress, and the level of treatment has also been continuously improved, but it still faces many challenges. The focus of research on the injury mechanism of TBI has gradually shifted from the classic signaling pathways of primary injury to the study of secondary injury mechanisms. Pharmacological research on various therapeutic targets has also made significant progress, which is expected to be transformed into new TBI therapeutic drugs. On the other hand, many new clinical concepts, new systems, and new methods are constantly being integrated into the diagnosis and treatment of TBI, which has gradually transformed from the original treatment of acute neurological injury to the comprehensive treatment of chronic systemic diseases. This paper is based on the latest research progress in the basic and clinical aspects of TBI, and provides a review of its current status and development trends, providing reference for the medical treatment and research of TBI.

Implementation of a strengths-based approach in a traumatic brain injury community service; perspectives of community workers.

Background The strengths-based approach (SBA) was initially developed for people living with mental health issues but may represent a promising support option for community participation of people living with a traumatic brain injury (TBI). A community-based organisation working with people living with TBI is in the process of adapting this approach to implement it in their organisation. No studies explored an SBA implementation with this population. This study explores the implementation of key components of the SBA in a community-based organisation dedicated to people living with TBI. Methods A qualitative descriptive design using semi-structured interviews (n = 10) with community workers, before and during implementation, was used. Transcripts were analysed inductively and deductively. Deductive coding was informed by the SBA fidelity scale. Results Group supervision and mobilisation of personal strengths are key SBA components that were reported as being integrated within practice. These changes led to improved team communication and cohesiveness in and across services, more structured interventions, and greater engagement of clients. No changes were reported regarding the mobilisation of environmental strengths and the provision of individual supervision. Conclusion The implementation of the SBA had positive impacts on the community-based organisation. This suggests that it is valuable to implement an adaptation of the SBA for people living with TBI.

Trauma diagnostic-related target proteins and their detection techniques.

Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.

Social vulnerability and traumatic brain injury hospitalizations from sports and recreation among pediatric patients in the United States.

PURPOSE: This study examined the associations between individual as well as neighborhood social vulnerability and sports and recreation-related traumatic brain injury (SR-TBI) hospitalizations among pediatric patients in the U.S. METHODS: We obtained 2009, 2010 and 2011 hospitalization data in the U.S. from the National Inpatient Sample (NIS) database, linked it to 2010 neighborhood social vulnerability index (SVI) data from the Centers for Disease Prevention and Control (CDC), and assigned U.S. hospitals to one of four SVI quartiles. SR-TBI outcomes studied include: odds of hospitalization, length of stay (LOS), and discharge to post-acute care (DTPAC). RESULTS: We found associations between race/ethnicity and all SR-TBI outcomes; however, sex, primary payer, and neighborhood overall SVI were only associated with LOS. Compared to White children, Native American children had almost three times higher odds of hospitalization for SR-TBI (OR: 2.82, 95% CI: 1.30, 6.14), 27% longer LOS (ß: 27.06, 95% CI: 16.56, 38.51), but 99.9% lower odds of DTPAC (OR: 0.001, 95% CI: 0.00, 0.01). Compared to children with private insurance, children with public insurance had 11% longer LOS (ß: 10.83, 95% CI: 8.65, 13.05). Hospitalization in neighborhood with higher overall SVI was associated with longer LOS (p < 0.0001). CONCLUSIONS: These findings suggest that individual and neighborhood social vulnerability can have a significant impact on the health outcomes of children, especially in the context of SR-TBI.

Efficacy of a virtual reality-based cognitive interactive training program for children with traumatic brain injuries: study protocol for a parallel-group randomized controlled trial.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of disability in children. Cognitive rehabilitation for this population is critical for their long-term health outcomes. This trial aims to evaluate the efficacy of a virtual reality-based program (VICT) for training executive functions in children with TBI. METHODS: A parallel group randomized controlled trial will be conducted among up to 32 children with TBI. Children in the intervention group will receive the VICT training while children in the control group will play a comparable VR game without executive function training. Each participant will be assessed at baseline, post-intervention, and 1-month follow-up. Outcomes will include core executive functions, attention, and health-related quality of life measured by computerized tasks or standardized questionnaires. DISCUSSION: Cognitive rehabilitation is among the top healthcare needs for pediatric TBI patients. Virtual reality-based training is promising due to its versatile content, flexibility, and potential cost savings for both patients and providers. Findings of this trial will provide data on the efficacy of the VICT program on core executive functions, attention problems, and health-related quality of life and serve as the empirical foundation for future larger multi-site effectiveness trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04526639 . Registered on August 18, 2020.

dTBI2: A Calibrated, Tunable Device for Administering Traumatic Brain Injury in Drosophila.

The second-generation Drosophila traumatic brain injury (TBI) device dTBI2 improves Drosophila TBI administration by providing a moderate-throughput, tunable, head-specific injury. Our updated device design improves user-friendliness, eliminates inconsistencies in injury timing, and has an updated circuit design to extend the longevity of delicate electronic components. dTBI2 improves reproducibility across users and runs, and results in more consistent post-injury phenotypes. This protocol describes the construction, calibration, and use of the dTBI2 device, which uses an Arduino-controlled piezoelectric actuator to deliver a force that compresses a fly head against a metal collar. The duration and depth of head compression is tunable, allowing calibration of injury severity. All device components are commercially available, and the entire device can be constructed in under a week for less than $1000. The dTBI2 design will enable any lab to build a highly reliable, low-cost device for Drosophila TBI, facilitating increased adoption and ease of exploration of closed-head TBI in Drosophila for forward genetic screens. We describe below the three protocols necessary for constructing a dTBI2 device. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Construction of the dTBI2 control device Basic Protocol 2: Construction of the piezoelectric actuator housing Basic Protocol 3: Administration of dTBI2 injuries.

[The secretome of mesenchymal stromal cells as a new hope in the treatment of acute brain tissue injuries]. / Sekretom mezenkhimnykh stromal'nykh kletok kak novaya nadezhda v lechenii ostrykh povrezhdenii golovnogo mozga.

Ischemic and hemorrhagic strokes, traumatic brain injury, bacterial and viral encephalitis, toxic and metabolic encephalopathies are very different pathologies. But, they have much more in common than it might seem at first glance. In this review, the authors propose to consider these brain pathologies from the point of view of the unity of their pathogenetic mechanisms and approaches to therapy. Particular attention is paid to promising therapeutic approaches, such as therapy using cells and their secretion products: an analysis of the accumulated experimental data, the advantages and limitations of these approaches in the treatment of brain damage was carried out. The review may be of interest both to specialists in the field of neurology, neurosurgery and neurorehabilitation, and to readers who want to learn more about the progress of regenerative biomedicine in the treatment of brain pathologies.

IMproving psYchosocial adjustment to Traumatic Brain Injury from acute to chronic injury through development and evaluation of the myTBI online psychoeducation platform: protocol for a mixed-methods study.

INTRODUCTION: This protocol describes the myTBI study which aims to: (1) develop an online psychoeducation platform for people with traumatic brain injury (TBI), their family members/caregivers, and healthcare staff to improve psychosocial adjustment to TBI across different phases of injury (acute, postacute, and chronic), and (2) undertake an evaluation of efficacy, acceptability, and feasibility. METHODS AND ANALYSIS: A three-stage mixed-methods research design will be used. The study will be undertaken across four postacute community-based neurorehabilitation and disability support services in Western Australia. Stage 1 (interviews and surveys) will use consumer-driven qualitative methodology to: (1) understand the recovery experiences and psychosocial challenges of people with TBI over key stages (acute, postacute, and chronic), and (2) identify required areas of psychosocial support to inform the psychoeducation platform development. Stage 2 (development) will use a Delphi expert consensus method to: (1) determine the final psychoeducation modules, and (2) perform acceptance testing of the myTBI platform. Finally, stage 3 (evaluation) will be a randomised stepped-wedge trial to evaluate efficacy, acceptability, and feasibility. Outcomes will be measured at baseline, postintervention, follow-up, and at final discharge from services. Change in outcomes will be analysed using multilevel mixed-effects modelling. Follow-up surveys will be conducted to evaluate acceptability and feasibility. ETHICS AND DISSEMINATION: Ethics approval was granted by North Metropolitan Health Service Mental Health Research Ethics and Governance Office (RGS0000005877). Study findings will be relevant to clinicians, researchers, and organisations who are seeking a cost-effective solution to deliver ongoing psychoeducation and support to individuals with TBI across the recovery journey. TRIAL REGISTRATION NUMBER: ACTRN12623000990628.

Exploring Heparan Sulfate Proteoglycans as Mediators of Human Mesenchymal Stem Cell Neurogenesis.

Alzheimer's disease (AD) and traumatic brain injury (TBI) are major public health issues worldwide, with over 38 million people living with AD and approximately 48 million people (27-69 million) experiencing TBI annually. Neurodegenerative conditions are characterised by the accumulation of neurotoxic amyloid beta (Aß) and microtubule-associated protein Tau (Tau) with current treatments focused on managing symptoms rather than addressing the underlying cause. Heparan sulfate proteoglycans (HSPGs) are a diverse family of macromolecules that interact with various proteins and ligands and promote neurogenesis, a process where new neural cells are formed from stem cells. The syndecan (SDC) and glypican (GPC) HSPGs have been implicated in AD pathogenesis, acting as drivers of disease, as well as potential therapeutic targets. Human mesenchymal stem cells (hMSCs) provide an attractive therapeutic option for studying and potentially treating neurodegenerative diseases due to their relative ease of isolation and subsequent extensive in vitro expansive potential. Understanding how HSPGs regulate protein aggregation, a key feature of neurodegenerative disorders, is essential to unravelling the underlying disease processes of AD and TBI, as well as any link between these two neurological disorders. Further research may validate HSPG, specifically SDCs or GPCs, use as neurodegenerative disease targets, either via driving hMSC stem cell therapy or direct targeting.

Genetic Contributions to Recovery following Brain Trauma: A Narrative Review.

Traumatic brain injury (TBI) is a frequently encountered form of injury that can have lifelong implications. Despite advances in prevention, diagnosis, monitoring, and treatment, the degree of recovery can vary widely between patients. Much of this is explained by differences in severity of impact and patient-specific comorbidities; however, even among nearly identical patients, stark disparities can arise. Researchers have looked to genetics in recent years as a means of explaining this phenomenon. It has been hypothesized that individual genetic factors can influence initial inflammatory responses, recovery mechanisms, and overall prognoses. In this review, we focus on cytokine polymorphisms, mitochondrial DNA (mtDNA) haplotypes, immune cells, and gene therapy given their associated influx of novel research and magnitude of potential. This discussion is prefaced by a thorough background on TBI pathophysiology to better understand where each mechanism fits within the disease process. Cytokine polymorphisms causing unfavorable regulation of genes encoding IL-1ß, IL-RA, and TNF-α have been linked to poor TBI outcomes like disability and death. mtDNA haplotype H has been correlated with deleterious effects on TBI recovery time, whereas haplotypes K, T, and J have been depicted as protective with faster recovery times. Immune cell genetics such as microglial differentially expressed genes (DEGs), monocyte receptor genes, and regulatory factors can be both detrimental and beneficial to TBI recovery. Gene therapy in the form of gene modification, inactivation, and editing show promise in improving post-TBI memory, cognition, and neuromotor function. Limitations of this study include a large proportion of cited literature being focused on pre-clinical murine models. Nevertheless, favorable evidence on the role of genetics in TBI recovery continues to grow. We aim for this work to inform interested parties on the current landscape of research, highlight promising targets for gene therapy, and galvanize translation of findings into clinical trials.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

THE NEUROENDOTHELIAL AXIS IN TRAUMATIC BRAIN INJURY: MECHANISMS OF MULTIORGAN DYSFUNCTION, NOVEL THERAPIES, AND FUTURE DIRECTIONS.

ABSTRACT: Severe traumatic brain injury (TBI) often initiates a systemic inflammatory response syndrome, which can potentially culminate into multiorgan dysfunction. A central player in this cascade is endotheliopathy, caused by perturbations in homeostatic mechanisms governed by endothelial cells due to injury-induced coagulopathy, heightened sympathoadrenal response, complement activation, and proinflammatory cytokine release. Unique to TBI is the potential disruption of the blood-brain barrier, which may expose neuronal antigens to the peripheral immune system and permit neuroinflammatory mediators to enter systemic circulation, propagating endotheliopathy systemically. This review aims to provide comprehensive insights into the "neuroendothelial axis" underlying endothelial dysfunction after TBI, identify potential diagnostic and prognostic biomarkers, and explore therapeutic strategies targeting these interactions, with the ultimate goal of improving patient outcomes after severe TBI.

Effects of Transcranial Direct Current Stimulation on Motor and Cognitive Dysfunction in an Experimental Traumatic Brain Injury Model.

AIM: To investigate the therapeutic and neuroprotective effects of transcranial direct current stimulation (tDCS) application on the traumatic brain injury (TBI)-induced glutamate and calcium excitotoxicity and loss of motor and cognitive functions. MATERIAL AND METHODS: Forty rats were equally divided in the sham, TBI, tDCS + TBI + tDCS, and TBI + tDCS groups. Mild TBI was induced by dropping a 450-g iron weight from a height of 1 m onto the skull of the rats. The tDCS + TBI + tDCS group was prophylactically administered 1 mA stimulation for 30 min for 7 days starting 5 days before inducing TBI. In the TBI + tDCS group, tDCS (1 mA for 30 min) was administered 2 h after TBI, on days 1 and 2. Cognitive and locomotor functions were assessed using the novel object recognition and open field tests. The calcium, glutamate, and N-methyl-D-aspartate receptor 1 (NMDAR1) levels in the hippocampus were measured using enzyme-linked immunosorbent assay. RESULTS: Although the motor and cognitive functions were substantially reduced in the TBI group when compared with the sham, they improved in the treatment groups (p < 0.05). The calcium, glutamate, and NMDAR1 levels were considerably higher in the TBI group than in the sham (p < 0.001). However, they were considerably lower in the tDCS + TBI + tDCS and TBI + tDCS groups than in the TBI groups (p < 0.05). In particular, the change in the tDCS + TBI + tDCS group was higher than that in the TBI + tDCS group. CONCLUSION: Application of tDCS before the development of TBI improved motor and cognitive dysfunction. It demonstrated a neuroprotective and therapeutic effect by reducing the excitotoxicity via the regulation of calcium and glutamate levels.

Evaluation of canine adipose-derived mesenchymal stem cells for neurological functional recovery in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation. RESULTS: Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What's more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system. CONCLUSIONS: Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.