J. Neurotrauma [JOURNAL]
Sun
200 papers
Urinary Tract Infection Exaggerates Cognitive Deficits and Region-Specific Neuroinflammation Following Traumatic Brain Injury.
Zimomra Z, Lepak C, Boland R … +6 more , Taylor MA, McCraw A, Schreiber H, Crescenze I, McTigue DM, Kokiko-Cochran ON
J Neurotrauma · 2026 Jun · PMID 42357923 · Publisher ↗
Traumatic brain injury (TBI) increases the risk for infection, and urinary tract infection (UTI) is commonly reported in patient populations that require additional medical intervention. UTIs are one of the most prevalen...
Traumatic brain injury (TBI) increases the risk for infection, and urinary tract infection (UTI) is commonly reported in patient populations that require additional medical intervention. UTIs are one of the most prevalent bacterial infections worldwide, reflecting a significant public health threat that disproportionately affects females. UTIs are most often caused by uropathogenic (UPEC) and can cause delirium-like symptoms in vulnerable patients, but the specific neuroimmune and cognitive effects of post-injury UTI remain underexplored. To address this gap in knowledge, we present a unique combination of pre-clinical models of TBI and UTI to define the biological effects of bladder infection after brain injury. We hypothesize that UTI after TBI worsens the long-term outcome of brain injury. Female mice received either a sham injury or lateral fluid percussion TBI, and 3 days post-injury (DPI), mice were inoculated transurethrally with vehicle or UPEC to recapitulate a post-injury infection. Y-maze and open-field behavioral tests were administered 6 DPI and 8 DPI, respectively. Brains and blood were collected for flow cytometry and enzyme-linked immunosorbent assay from a subset of mice 6 DPI. Brains and urinary bladders were collected for immunohistochemistry from the remaining mice 10 DPI. TBI mice displayed spatial memory deficits, which were exacerbated following UTI; however, no differences in exploratory behavior were observed after TBI or UTI. TBI significantly elevated plasma interleukin-6, but strikingly, UTI following TBI dampened this response 6 DPI. Flow cytometry revealed no significant differences in circulating immune cells 6 DPI but confirmed that TBI elevated microglial reactivity and monocyte infiltration to the brain, independent of infection. TBI and UTI differentially modulated Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium-binding Adapter Molecule 1 (Iba1) expression in the hippocampus and cortex, reflecting additive and interaction-based effects. UTI after TBI elevated microglia CD68 expression in a brain region-specific manner further demonstrating that post-injury infection alters the neuroimmune landscape. Together, these data offer novel insight into the effects of UTI after TBI, showing that UTI after TBI is detrimental to overall outcome and warrant further investigation into the signaling mechanisms between bladder infection and neuroinflammation.
Fall Risk and Physical/Occupational Therapy Referral Patterns in Older Adults with Mild Traumatic Brain Injury.
Albrecht JS, Addison O, Dibble LE … +10 more , Orwig DL, Magaziner J, Newman M, Stevens D, Wickwire EM, Kozar R, Liang Y, Gruber-Baldini AL, Badjatia N, Fino PC
J Neurotrauma · 2026 Jun · PMID 42312554 · Publisher ↗
Falls are the primary cause of mild traumatic brain injury (mTBI) among older adults, yet limited research has examined patterns of clinical care, mobility, and subsequent fall risk in this population. The objective of t...
Falls are the primary cause of mild traumatic brain injury (mTBI) among older adults, yet limited research has examined patterns of clinical care, mobility, and subsequent fall risk in this population. The objective of this study was to evaluate outpatient physical or occupational therapy (PT/OT) referral patterns and assess physical function and fall risk status of older adults with mTBI. We analyzed acute care and 2-week post-mTBI assessment data from a prospective cohort study of adults aged 65 and older with mTBI treated at a level 1 trauma center and six affiliated hospitals 2023-2025 and meeting eligibility criteria. Of 625 that were confirmed eligible, 155 consented to participate in the study. Of these, five were missing the 2-week assessment and nine were missing PT/OT referral information, leaving 141 in the current study. The exposure of interest was referral to PT/OT at discharge, obtained from medical records. Two-week post-mTBI assessments included the Short Physical Performance Battery (SPPB) and the Four-Square Step Test (FSST). Statistical comparisons between exposure groups were made using Fisher's exact test, Student's -test or the Wilcoxon rank-sum test. Participants ( = 141) were on average 76.1 (standard deviation 7.3) years old and 56.0% female. Falls were the primary cause of mTBI (89%). At the 2-week assessment, participants demonstrated poor physical performance: 53% had impaired SPPB (<10), 62% had impaired FSST (>15 sec), and 65% had slow gait speeds (<0.80 m/s), all indicative of elevated fall risk. Only 34 (24%) were referred to PT/OT at discharge. Those referred were more likely to have received an inpatient PT/OT consultation (97% vs. 22%, < 0.001). Among participants not referred to PT/OT, 46% had impaired SPPB, 58% had impaired FSST, and 60% had slow gait speed, indicating high fall risk. Less than a quarter of older adults with primarily fall-related mTBI received any discharge PT/OT referral despite clear mobility and balance deficits. This critical gap in post-discharge rehabilitation underscores a disconnect between fall-prevention guidelines and clinical practice, leaving many older adults at high risk of recurrent falls and injuries.
The Effects of High-Thoracic Spinal Cord Injury on the Heart Transcriptome.
Fossey MPM, Hayes B, Erskine E … +6 more , Poormasjedi-Meibod MS, Haegert A, Sar F, Granville DJ, Singh A, West CR
J Neurotrauma · 2026 Jun · PMID 42311152 · Publisher ↗
It is becoming increasingly recognized that high-level spinal cord injury (SCI) is associated with altered heart structure and function, as well as a significantly elevated risk for heart disease. Despite this knowledge,...
It is becoming increasingly recognized that high-level spinal cord injury (SCI) is associated with altered heart structure and function, as well as a significantly elevated risk for heart disease. Despite this knowledge, we know remarkably little about the temporal molecular changes that occur in the heart following SCI and how these relate to functional decline. In the present study, we addressed this shortcoming by combining bulk RNA sequencing (RNA-seq) of left ventricle (LV) tissue with matching cardiac function assessments (i.e., pressure-volume loops obtained via LV catheterization) from the same animals. We studied rats at either the acute (1 and 3d post-SCI) or chronic (12wk post-SCI) stage of SCI to establish temporal patterns and compared findings to sham-injured rats. We found that SCI induces marked, time-dependent changes in cardiac gene expression and function. Acute (1-3d) and chronic (12w) SCI display distinct, often opposing transcriptomic signatures, with thousands of genes differentially expressed versus SHAM. Acute SCI is characterized by suppressed immune, inflammatory, cell cycle, and stress-response pathways with altered metabolism. Chronic SCI shows upregulated immune signaling, impaired oxidative phosphorylation, extracellular matrix remodeling, and stress responses. Functionally, cardiac systolic dysfunction occurs early post-SCI and persists to the chronic phase. Reduced systolic function is strongly correlated with changes in immune, hypoxia, and cholesterol-related genes at the acute timepoints and with immune and hormone-signaling pathways at the chronic timepoint. Collectively, our data provide novel insight into the cardiac transcriptome post-SCI and identify the molecular pathways that most strongly correlate with functional decline.
Rigor and Transparency in Two Neurotrauma-Publishing Journals: Editorial Policies Improve Transparent Reporting.
Bandrowski A, Namburi A, Ferguson A … +3 more , Floyd CL, Martone ME, PRECISE-TBI Investigators
J Neurotrauma · 2026 Jun · PMID 42306830 · Publisher ↗
Preclinical research in traumatic brain injury (TBI) continues to significantly increase knowledge and yield a large number of peer-reviewed studies, but translation of these results to the clinical setting has been mini...
Preclinical research in traumatic brain injury (TBI) continues to significantly increase knowledge and yield a large number of peer-reviewed studies, but translation of these results to the clinical setting has been minimal. Rigor and transparency factors such as concealment of group allocation (e.g., "blinding") or ensuring that reagents are identifiable are critical in ensuring that scientific studies are replicable and translatable. Yet, nearly all efforts aimed at measuring these factors have concluded that reporting practices are problematic and incomplete. One way to improve transparency of reporting practices is to require that authors address a set of transparency-related items in some way, such as a checklist or an article section. Recently, , a leading publisher of preclinical TBI research, instituted a required rigor-related section, which is explained to authors via a set of transparency, rigor, and reproducibility (TRR) instructions (one example for each article type). These documents include specific transparency sections explaining blinding, power calculations, protocols, code, and data deposition. is a journal that is similar in size, impact, and topic, but the journal does not have explicit instructions to authors about transparency items. The purpose of this study was to assess the degree to which transparency reporting items were included in published articles comparing reporting practices in the and . We used a commercial software, SciScore, which is an AI tool tuned to detect rigor/transparency sentences in published articles and count the number found (roughly dividing by the number expected) to obtain a score. Overall, SciScore found that in six of eight items that were explicitly asked for, such as power calculations, investigator blinding, inclusion criteria, attrition, and data, there were significant differences (more than 10%) compared to . However, in articles with the extra rigor section, three of four rigor items that were not explicitly asked for in the template rigor documents, such as subject demographics or transparent antibody reporting, were not different from . One item, reporting of the sex of subjects, was significantly better in This shows that the required rigor section is effective in improving reporting, but it would be far better if sex as a biological variable and transparent reporting of reagents (items present on major checklists, including NIH rigor criteria) would be included.
Neuroimaging and Fluid-Based Biomarkers in Sport-Related Concussion in Female Athletes: A Scoping Review.
Goeckner BD, Meyer E, Fry HM … +5 more , Ferreira E, Andersson MJ, O'Malley O, Mannix R, Meier TB
J Neurotrauma · 2026 Jun · PMID 42304867 · Publisher ↗
Sport-related concussion (SRC) is a significant public health concern, warranting exploration of neuroimaging and fluid-based biomarkers as objective measures for diagnosis and prognosis. Sex differences in concussion ou...
Sport-related concussion (SRC) is a significant public health concern, warranting exploration of neuroimaging and fluid-based biomarkers as objective measures for diagnosis and prognosis. Sex differences in concussion outcomes may be influenced by the menstrual cycle, hormones, and hormonal contraceptives. Equitable representation of female athletes in emerging biomarker research is critical, but existing literature may not meet this need. This scoping review assessed neuroimaging and fluid-based biomarker research in SRC for inclusion and analysis of female athletes and to summarize female-specific and sex-difference results. Searches in MEDLINE, Scopus, Cochrane, and PsycInfo from January 2001 to July 2025 identified original research published in English and focused on SRC with neuroimaging or fluid-based biomarker assessment within 6 months after injury. Studies were then classified based on study sample sex/gender, and studies with female-specific and sex-difference results were further summarized. Literature review revealed underrepresentation of concussed female athletes in biomarker research, with over three times more concussed male athletes studied than concussed female athletes and approximately 19 times more male-only than female-only studies. Most mixed-sex studies did not explicitly investigate female-specific results. The 29 summarized reports indicate potential sex differences and different results for female athletes than those in the broader existing literature, although small sample sizes make definitive conclusions difficult. Addressing the knowledge gap in SRC in female athletes requires future biomarker research to include sufficient numbers of female athletes, analyze data to identify potential sex differences, and collect relevant data, including hormone levels and detailed menstrual cycle and hormonal contraceptive use information.
Transcranial Photobiomodulation Promotes Neurological Resilience in Current Collegiate American Football Players Exposed to Repetitive Head Acceleration Events.
Lindsey HM, Esopenko C, Jain D … +13 more , Larson MJ, Johnson PK, Keleher F, Newsome MR, Goodrich-Hunsaker NJ, Mortensen B, Allen WD, Talbert LD, Hancock M, Davidson LE, Carr LS, Tate DF, Wilde EA
J Neurotrauma · 2026 Jun · PMID 42300020 · Publisher ↗
Repetitive head acceleration events (RHAE) are common in contact sports and associated with neuroinflammation, axonal injury, and long-term neurological impairments, including increased risk for chronic traumatic encepha...
Repetitive head acceleration events (RHAE) are common in contact sports and associated with neuroinflammation, axonal injury, and long-term neurological impairments, including increased risk for chronic traumatic encephalopathy. Current strategies for addressing RHAE focus on post-injury care rather than proactive neuroprotection, leaving athletes vulnerable to cumulative neurotrauma. Transcranial photobiomodulation (PBM) has shown promise in reducing neuroinflammation and promoting neuroprotection in traumatic brain injury; however, its potential to mitigate the structural brain changes associated with RHAE in actively competing athletes has not been investigated. The aim of this study was to investigate whether PBM mitigates RHAE-related neuroinflammatory and microstructural changes in collegiate American football players over a single National Collegiate Athletic Association Division I season. We hypothesized that restricted diffusion imaging (RDI) and quantitative anisotropy (QA), diffusion magnetic resonance imaging markers of neuroinflammation and axonal remodeling, respectively, would increase in the Sham PBM group due to RHAE exposure but remain stable in the Active PBM group, indicating neurological resilience. Twenty-six collegiate football players were randomly assigned to Active ( = 13) or Sham ( = 13) PBM groups. PBM (810 nm) was self-administered 3 days a week under supervision in the athletic training room with a transcranial plus intranasal device throughout the preseason practice period and regular season (16 weeks). Diffusion MRI data were collected pre- and postseason, and correlational tractography was used to assess the effects of PBM on longitudinal changes in RDI and QA. Moderation analyses examined time × group interactions, with post hoc analyses exploring within- and between-group differences in RDI and QA cross-sectionally and longitudinally. Correlational tractography revealed significant main effects and interactions of time and group, with widespread increases in RDI and QA observed in the Sham PBM group over the season, consistent with neuroinflammation and axonal remodeling. In contrast, the Active PBM group showed relative stability in RDI and QA over time, with significant reductions observed in some areas. These findings suggest that PBM may mitigate ongoing neuroinflammation and facilitate the recovery processes. This study provides the first evidence suggesting that transcranial PBM reduces neuroinflammatory and axonal injury markers in American collegiate football players over a single season. PBM may serve as a noninvasive and accessible intervention for mitigating the cumulative neurological effects of RHAE exposure, offering a neuroprotective strategy for athletes participating in collision and contact sports. Future research should examine the long-term benefits of PBM across multiple seasons and its impact on functional outcomes to further establish the role of PBM in athlete brain health and wellness.
Brain-Derived Proteins Induce Autoimmune Responses via MBP-IgG Immune Complexes and Participate in Pulmonary Edema Following Traumatic Brain Injury.
Shi Q, Hu TT, Liang B … +5 more , Fang YH, Xu LX, Chen L, Tong XG, Yan H
J Neurotrauma · 2026 Jun · PMID 42300019 · Publisher ↗
Neurogenic pulmonary edema (NPE) is a complication that often affects patients following central nervous system (CNS) injury. Nevertheless, the complex relationship between CNS injury and NPE initiation and progression r...
Neurogenic pulmonary edema (NPE) is a complication that often affects patients following central nervous system (CNS) injury. Nevertheless, the complex relationship between CNS injury and NPE initiation and progression remains unclear. Here, we show that the leakage of brain proteins (BPs) following traumatic brain injury results in the formation of immune complexes and lung edema. Quantitative proteomic analysis revealed that BP preferentially affected the Kng1/SPHK2/S1P pathway. We treated rats with the S1P receptor antagonist fingolimod or conventional steroid drugs and showed that this was sufficient to attenuate the severity of pulmonary and related pathological changes. These results provide novel evidence that the immune complexes induced by BPs are deposited in the lung tissue, activating a series of inflammatory reactions that culminate in pulmonary edema. Considering these results, we propose the innovative concept of "neuroimmunogenic pulmonary edema" as a relevant pathological entity.
Thalamic Structural Connectivity and Cognitive Outcome in the Subacute Period Following Mild Traumatic Brain Injury.
Baird ME, Yang JY, Seal ML … +2 more , Beare R, Anderson JFI
J Neurotrauma · 2026 Jun · PMID 42300018 · Publisher ↗
Emerging evidence suggests the thalamus may be a relevant structure in mild traumatic brain injury (mTBI). However, the structural connectivity profile of the thalamus has not been investigated in mTBI, nor have thalamic...
Emerging evidence suggests the thalamus may be a relevant structure in mild traumatic brain injury (mTBI). However, the structural connectivity profile of the thalamus has not been investigated in mTBI, nor have thalamic contributions to cognitive function been characterized in this population. This study investigated the relative strength of connectivity from thalamic subregions following mTBI and subsequently studied the associations between these metrics and cognitive performance. The final analyzed dataset included 39 mTBI patients and 28 trauma control (TC) patients aged 18-60 years, who were recruited following hospital admission for physical injury. Participants completed a magnetic resonance imaging (MRI) protocol including both structural MRI and multishell diffusion-weighted MRI sequences at 6-12 weeks (mean = 57 days, standard deviation = 11) post-injury. Thalamic segmentations were combined with cortical and subcortical parcellations to define nodes of each participant's structural connectivity network. Connectivity matrices were generated by mapping streamline reconstruction onto the 179 parcels. Nodal edge strength, representing the weighted connections of thalamic subregion edges, was calculated. Participants also completed a range of cognitive tests examining processing speed, attention, memory, and executive functions. The two groups were comparable with respect to thalamic subregion edge strength and performance on cognitive tests. These primary findings suggest that nodal structural connectivity of the thalamus is normal at this time point following injury. Moderation analysis revealed several interactions between group and edge strength predicting cognitive performance, namely, increased edge strength generally predicted better cognitive performance in the TC group, but worse performance in the mTBI group. These preliminary findings require further validation, although they raise the question as to whether sustaining an mTBI results in a change in the relationship between thalamic structure and cognitive function 6-12 weeks after injury.
What Is Your Model Predicting? The Need to Develop Useful Clinical Prediction Models in Neurotrauma.
Torres-Espin A, Fehlings MG
J Neurotrauma · 2026 Jun · PMID 42249687 · Publisher ↗
Abstract loading — click title to view on PubMed.
Metabolic Dysregulation in Traumatic Brain Injury: Mechanisms, Clinical Implications, and Therapeutic Opportunities.
Ali A, Hussain MS, Ahmed ME … +2 more , Giri S, Ahmad AS
J Neurotrauma · 2026 Jun · PMID 42233441 · Publisher ↗
Traumatic brain injury (TBI) affects millions globally each year, often resulting in long-term health issues or death. While the immediate physical damage caused by these injuries receives much attention, subsequent meta...
Traumatic brain injury (TBI) affects millions globally each year, often resulting in long-term health issues or death. While the immediate physical damage caused by these injuries receives much attention, subsequent metabolic changes in the brain are equally vital to recovery but understudied. After TBI, brain energy regulation and consequential metabolic processes are disrupted. This review provides a detailed examination of metabolic alterations following TBI, including glucose and lipid processing disruptions, increased lactate levels, neurotransmitter imbalances, and oxidative stress. These changes can lead to hyper/hypoglycemia, lactate accumulation, chemical imbalances, and heightened oxidative stress, all of which impede recovery. Understanding these biochemical shifts is essential for developing more effective treatments. This review offers a comprehensive overview of brain metabolic changes post-TBI and discusses some promising therapies, including drugs, nutrition, and lifestyle adjustments, that could aid recovery and improve the quality of life of those impacted.
Ventriculoperitoneal Versus Lumboperitoneal Shunt for Post-Hemorrhagic Hydrocephalus: A Multicenter Analysis.
Sun T, Yuan Y, You C … +3 more , Zhang L, Wu K, Guan J
J Neurotrauma · 2026 May · PMID 42219963 · Publisher ↗
Ventriculoperitoneal shunt (VPS) is the cornerstone therapy for post-hemorrhagic hydrocephalus (PHH). The optimal shunt strategy for PHH remains inconclusive, as the long-term outcomes of VPS and lumboperitoneal shunt (L...
Ventriculoperitoneal shunt (VPS) is the cornerstone therapy for post-hemorrhagic hydrocephalus (PHH). The optimal shunt strategy for PHH remains inconclusive, as the long-term outcomes of VPS and lumboperitoneal shunt (LPS) are not definitive. This study compared the long-term efficacy and safety of VPS versus LPS and identified specific risk factors for shunt failure in each treatment group. We conducted a retrospective cohort study of adult PHH patients undergoing VPS or LPS at four tertiary centers between 2014 and 2018. The primary outcome was the shunt failure rate at 3 years. Secondary outcomes included complications, the Evans index, and the modified Rankin Scale (mRS) score. To identify risk factors for failure, we performed univariate and multivariate binary logistic regression analyses, stratifying by shunt type. Of the 273 included patients (VPS: 177, LPS: 96), the VPS group demonstrated a significantly lower 3-year shunt failure rate (15.3% vs. 27.1%, = 0.018) and a higher proportion of favorable outcomes (mRS ≤ 3: 86.4% vs. 72.9%, = 0.006). Overdrainage was more frequent in the LPS group (12.5% vs. 5.1%, = 0.028). Multivariate analysis revealed that longer time from hemorrhage to surgery (odds ratio [OR]: 1.143, = 0.020), elevated cerebrospinal fluid (CSF) protein (OR: 9.003, < 0.001), and low CSF glucose (OR: 0.458, = 0.046) were independent risk factors for VPS failure. For LPS, the presence of CSF red blood cells was the sole independent predictor of failure (OR: 12.514, = 0.019). In conclusion, this study suggests that VPS is associated with superior long-term efficacy and a lower risk of overdrainage compared to LPS in managing PHH. The risk profiles for shunt failure differ between the two procedures, necessitating distinct pre-operative considerations.
Screen Time after Concussion: Still Searching for Just Right.
Macnow T, Mannix R
J Neurotrauma · 2026 May · PMID 42204942 · Publisher ↗
Abstract loading — click title to view on PubMed.
Traumatic Brain Injury and High Combat Exposure Pose Additive Risk for Specific Chronic Health Conditions in Veterans Affairs Million Veteran Program Enrollees.
Verkuilen AC, Talbert LD, Valocchi E … +4 more , Kodama L, Chanfreau-Coffinier C, VA Million Veteran Program (MVP),, Merritt VC
J Neurotrauma · 2026 May · PMID 42198943 · Publisher ↗
Traumatic brain injury (TBI) and combat exposure are common experiences among U.S. military Veterans, each linked to a wide array of chronic health conditions. Prior studies have tended to evaluate these risk factors sep...
Traumatic brain injury (TBI) and combat exposure are common experiences among U.S. military Veterans, each linked to a wide array of chronic health conditions. Prior studies have tended to evaluate these risk factors separately; thus, their combined influence on health outcomes remains unknown. In particular, research has not systematically examined whether TBI and combat exposure interact to exacerbate risk for poor long-term outcomes, limiting our understanding of how these co-occurring experiences shape Veterans' health. This study aimed to investigate whether TBI and high combat exposure interact to exacerbate risk for chronic health conditions in Veterans. Data were drawn from 156,242 Veterans enrolled in the VA Million Veteran Program (MVP; mean age = 64.8 years [standard deviation = 12.2], 95.1% male). TBI status was determined using self-report on the MVP Baseline Survey, and combat exposure (high vs. other) was assessed using the Combat Experiences Scale of the Deployment Risk and Resilience Inventory, administered as part of the MVP Lifestyle Survey. Health outcomes included self-reported mental health/psychiatric, cardiovascular, and neurological conditions, assessed via the MVP Baseline Survey. Multivariate logistic regressions tested associations of TBI and combat exposure with each outcome, adjusting for age, sex, race, ethnicity, and service era. Additive-scale interactions were evaluated using the relative excess risk due to interaction (RERI) statistic. Veterans with a history of TBI had significantly greater odds of reporting all psychiatric, cardiovascular, and neurological conditions evaluated (odds ratios [ORs] = 1.17-6.43). High combat exposure was also significantly associated with increased odds of experiencing all psychiatric conditions and several cardiovascular and neurological conditions (ORs = 1.11-3.24). RERI analyses showed significant interactions between TBI and high combat exposure for several psychiatric and neurological conditions (RERI = 0.27-4.70), indicating that the increased probability of those conditions was even greater for Veterans with both TBI history and high combat exposure. Altogether, results showed that both TBI and high combat exposure were independently associated with increased risk for endorsing a variety of chronic health conditions. In addition, their combined exposure resulted in even greater risk for several psychiatric and neurological conditions. These findings highlight the importance of evaluating combined risk factors pertinent to Veteran health to better identify those at risk for chronic health conditions.
Platelet Substitute Mitigates Coagulopathy and Improves Survival of Rats with Traumatic Brain Injury Induced by Laser-Induced Shockwave.
Sasa R, Hagisawa K, Kinoshita M … +5 more , Hotta M, Takeoka S, Kawauchi S, Sato K, Tomura S
J Neurotrauma · 2026 May · PMID 42178722 · Publisher ↗
Traumatic brain injury (TBI) is frequently complicated by coagulopathy, characterized by a complex interaction between hypercoagulability and hyperfibrinolysis. TBI-induced coagulopathy is a critical factor in neurologic...
Traumatic brain injury (TBI) is frequently complicated by coagulopathy, characterized by a complex interaction between hypercoagulability and hyperfibrinolysis. TBI-induced coagulopathy is a critical factor in neurological deterioration, resulting in poor prognoses. Despite recent advances in the clinical management of TBI, few effective therapies are available for TBI-induced coagulopathy. Tranexamic acid (TXA) and various concentrates of coagulation factors are ineffective because these agents promote secondary rather than primary hemostasis. Currently, only platelet concentrates are involved in the formation of platelet clots for primary hemostasis. We aimed to develop H12-(adenosine 5'-diphosphate [ADP])-liposomes, a novel platelet substitute. This platelet-targeted hemostatic agent comprises liposomes with the H12 peptide, which selectively binds to activated platelets and encapsulates ADP to locally promote platelet activation and thrombus formation, subsequently halting bleeding. Similar to platelet concentrates, H12-(ADP)-liposomes can promote primary hemostasis. To elucidate the effects of H12-(ADP)-liposome treatment on TBI and TBI-induced coagulopathy, an appropriate animal model of TBI-induced coagulopathy is required. As only few reliable models are available, we established a novel rat model of TBI-induced coagulopathy induced by laser-induced shockwave (LISW) exposure. This model did not require surgical craniotomy and allowed us to focus on TBI-induced coagulopathy. In this model, expansion of the intracranial hematoma volume within 30 min of LISW exposure was the determining factor for mortality. The 24-h survival rate of LISW-exposed animals was 70.3% (26 of 37 rats). In this model, treatment with TXA showed a modest potential to rescue animals from TBI owing to its antifibrinolytic effects. However, TXA did not improve endothelial injury or prevent coagulopathy. In contrast, treatment with H12-(ADP)-liposomes after LISW exposure prevented endothelial injury and expansion of intracranial hematoma. H12-(ADP)-liposome treatment also prevented prolongation of the prothrombin time after 16 h of LISW exposure. Consequently, this treatment significantly improved the acute prognosis of LISW-exposed animals. These findings demonstrate that our LISW-based TBI model replicates the essential aspects of TBI-induced coagulopathy and that H12-(ADP)-liposomes have therapeutic potential for mitigating trauma-induced coagulopathy and improving TBI outcomes.
Novel Psychiatric Disorders Following Mild Traumatic Brain Injury in the Second Year of the Adolescent Brain Cognitive Development Study.
Troyer EA, Meng W, Vaida F … +11 more , Delfel E, Jacobus J, de Souza NL, Dennis EL, Wilde EA, Abildskov T, Cheng M, Yang X, Hesselink JR, Bigler ED, Max JE
J Neurotrauma · 2026 May · PMID 42157479 · Publisher ↗
Pediatric mild traumatic brain injury (mTBI) is common and can potentially lead to novel psychiatric disorders (NPDs). However, the psychiatric sequelae of mTBI in community-dwelling children require further study. NPDs...
Pediatric mild traumatic brain injury (mTBI) is common and can potentially lead to novel psychiatric disorders (NPDs). However, the psychiatric sequelae of mTBI in community-dwelling children require further study. NPDs were characterized during the first 2 years following injury in children with a first lifetime mTBI between 9 and 11 years of age in the Adolescent Brain Cognitive Development study ( = 99), compared with orthopedically injured ( = 380) and noninjured ( = 374) controls. Outcomes were defined as NPD-Any (NPD-A), which included all NPDs with onset during the study period, and NPD-Current (NPD-C), which included only those NPDs that were still active at the follow-up study visit. Possible confounders, including injury and non-injury-related factors, were also considered. NPDs were common at the year 2 study visit, particularly anxiety disorders, but rates were similar across injury groups. Mild TBI was not associated with differential odds of NPD. However, family psychiatric history predicted greater odds of NPD (for NPD-C, odds ratio [OR] = 1.345; 95% confidence interval [CI] = 1.124-1.615; < 0.001; for NPD-A, OR = 1.217; 95% CI = 1.078-1.375; = 0.002), and pre-injury psychiatric disorder was associated with increased risk of NPD at year 2 (for NPD-C, OR = 1.557; 95% CI = 1.022-2.346; = 0.037; for NPD-A, OR = 1.568; 95% CI = 1.198-2.055, = 0.001). In this representative community-dwelling sample of children in the United States who experienced a first lifetime mTBI between 9 and 11 years of age, mTBI was not associated with risk for NPDs in the first 2 years following injury. However, non-injury-related factors, including family psychiatric history and pre-injury psychiatric disorders, were associated with NPDs.
Improving Data Quality in Neurotrauma Data Sharing: The Open Data Commons Minimal Data Standards and a Data Tool for Compliance.
Fond KA, Radabaugh H, Vavrek R … +10 more , Axtman PJ, Huie JR, Fedor BA, Gensel JC, Fouad K, Grethe JS, Martone ME, Ferguson AR, Torres-Espin A, PRECISE-TBI Investigators†
J Neurotrauma · 2026 May · PMID 42157403 · Publisher ↗
The Open Data Commons (ODC) for Traumatic Brain Injury (ODC-TBI) and Spinal Cord Injury (ODC-SCI) are secure online platforms for members of the neurotrauma community to access curated, publicly available domain-specific...
The Open Data Commons (ODC) for Traumatic Brain Injury (ODC-TBI) and Spinal Cord Injury (ODC-SCI) are secure online platforms for members of the neurotrauma community to access curated, publicly available domain-specific data, and manage, share, and publish datasets with a citable DOI. Currently, preparing and uploading a dataset and its corresponding data dictionary involve multiple rounds of manual revisions to meet ODC guidelines. Here, we present the ODC Minimum Data Standards (MDS) and the ODC Data Quality App (ODCdqa), an open-source web-based tool that simplifies the revision and curation workflow. The ODCdqa allows users to automate initial data quality checks and provides immediate feedback on whether the dataset meets ODC data specifications or requires edits. All publicly available datasets on the ODC-SCI and ODC-TBI websites were passed into the ODCdqa for analysis. Exclusion criteria were: (1) did not have a data dictionary, and (2) the dataset and/or data dictionary had different headers. The aggregated results were then used to identify common areas of difficulty and inform the future directions of ODC tool development and platform. Out of the 124 publicly available ODC datasets uploaded between 2018 and September 2025, 119 were used (84 from ODC-SCI, 35 from ODC-TBI). Both ODC-SCI and ODC-TBI had a trend of reducing the number of failed checks as the platform matured over the years, and the MDS and ODCdqa were used regularly by curators and users. In summary, the ODCdqa is an automated tool that allows any user to perform initial checks to determine whether a dataset and its corresponding data dictionary are ready for upload to the ODC platform. As the ODC platform evolves, more checks and features will be added to the ODCdqa.
Increased Cholinergic Activity in Mild Traumatic Brain Injury: Preliminary Evidence from [F]FEOBV PET Study.
Shvetz C, Saint-Georges Z, Hamati R … +6 more , Marshall S, Holahan M, Joutsa J, Tremblay S, Guimond S, Tuominen L
J Neurotrauma · 2026 May · PMID 42152806 · Publisher ↗
Mild traumatic brain injury (mTBI) is a prevalent condition. While symptoms typically resolve within a few weeks, a subset of individuals experience persistent cognitive symptoms. It is not known why symptoms persist in...
Mild traumatic brain injury (mTBI) is a prevalent condition. While symptoms typically resolve within a few weeks, a subset of individuals experience persistent cognitive symptoms. It is not known why symptoms persist in some individuals. Cholinergic projections from the basal forebrain (BF) support attention and memory and may be affected in mTBI. Therefore, we investigated putative BF cholinergic alterations in chronic mTBI using [F]fluoroethoxybenzovesamicol ([F]FEOBV) positron emission tomography (PET) and examined associations with cognitive performance. Ten individuals with chronic mTBI (≥1-year post-injury) and 23 healthy controls underwent [F]FEOBV PET imaging to assess vesicular acetylcholine transporter (VAChT) levels in the BF and completed cognitive testing. We found significantly increased [F]FEOBV uptake in the BF of mTBI participants ( = 4.84, SD = 0.48) relative to controls ( = 4.54, SD = 0.36, = 0.043). In mTBI, greater [F]FEOBV uptake correlated with faster processing speed ( = 0.014). mTBI participants performed worse than controls on all cognitive tests, with the largest group differences in working memory ( = -0.84), executive function ( = -0.65), and processing speed ( = -0.53). This study is the first to evaluate cholinergic changes following mTBI in human participants. mTBI was associated with increased cholinergic functions in the BF. As greater VAChT levels were linked to better cognitive performance in the mTBI sample, this finding may reflect cholinergic compensation in chronic mTBI.
Bridging Trauma and Parkinson's Disease: Mechanisms, Models, and Biomarkers of Post-Traumatic Parkinsonism.
Satyaprakash SA, Gupta NK, Singh S … +2 more , Gupta RK, Singh SP
J Neurotrauma · 2026 May · PMID 42152803 · Publisher ↗
One of the most prevalent neurodegenerative diseases, Parkinson's disease (PD), is generally discussed in terms of aging, genetic predisposition, and environmental exposures. Nonetheless, there is growing evidence that b...
One of the most prevalent neurodegenerative diseases, Parkinson's disease (PD), is generally discussed in terms of aging, genetic predisposition, and environmental exposures. Nonetheless, there is growing evidence that both isolated severe traumatic events and repetitive mild traumatic brain injury may play a significant role in the development of parkinsonian features. This trauma-associated condition, known as Post-Traumatic Parkinsonism Syndrome (PTPS), is becoming more widely acknowledged as a clinically significant but underdiagnosed illness. The differences between PTPS and conditions like chronic traumatic encephalopathy (CTE) are often blurred because, in contrast to idiopathic PD, PTPS typically manifests after a specified latency period following head injury and is often accompanied by overlapping symptoms of cognitive, behavioral, and motor dysfunction. At the pathophysiological level, PTPS is defined by the combination of trauma-induced processes, such as neuroinflammation, axonal injury, and dysregulated acetylation pathways, with mechanisms known to be associated with PD, such as alpha-synuclein aggregation, dopaminergic neuronal loss, and impaired protein clearance. Today, experimental models demonstrate how trauma speeds up or even starts neurodegenerative cascades, providing a unique platform to investigate disease mechanisms outside of the traditional toxin-based paradigms of PD. The current understanding of PD, PTPS, and CTE is summarized in this review, with a focus on risk factors, comparative pathology, and experimental model translational insights. This review emphasizes the significance of acknowledging trauma as more than a trigger but rather as a potential contributor to long-term neurodegeneration and disability by presenting PTPS as a unique but related syndrome within the PD spectrum.
3.5/6SH: Multicenter Real-World Derivation and External Validation of a CT-Based Formula for Chronic Subdural Hematoma Volume Estimation.
Liu T, Zhao B, Liu Y … +5 more , Xie L, Wang D, Zhao Z, Zhang J, Jiang R
J Neurotrauma · 2026 Jan · PMID 42149104 · Full text
Accurate hematoma volume estimation in chronic subdural hematoma (cSDH) is crucial for clinical decision-making. The commonly used 1/2ABC formula, originally developed for small, regular hematomas, may be inaccurate for...
Accurate hematoma volume estimation in chronic subdural hematoma (cSDH) is crucial for clinical decision-making. The commonly used 1/2ABC formula, originally developed for small, regular hematomas, may be inaccurate for cSDH due to its irregular morphology. A rapid, reliable, and practical method for bedside assessment is needed. This analysis of a multicenter, real-world study compared seven simplified computed tomography-based formulas with volumetric measurements obtained using three-dimensional (3D) Slicer in a derivation cohort of 129 patients with cSDH. We further evaluated the newly proposed 3.5/6SH formula in an independent validation cohort of 60 additional patients. Accuracy, agreement, and efficiency were evaluated using estimation error, percentage deviation, intraclass correlation coefficients (ICCs), and Bland-Altman (BA) analysis. In the derivation cohort, the 3.5/6SH formula yielded the lowest median volume deviation (-0.82 mL, interquartile range [IQR] 13.12 mL), the smallest percentage deviation (-1.00%, IQR 17.08%), and the highest ICC (0.973), indicating high accuracy and close agreement with the 3D Slicer reference standard. In contrast, the widely used 1/2ABC formula exhibited a larger negative percentage deviation (-4.64%) and a lower ICC (0.910). BA analysis further confirmed that 3.5/6SH had the narrowest limits of agreement and a clinically acceptable maximum absolute percentage deviation (29.33%), whereas the maximum deviation for 1/2ABC (65.04%) exceeded the clinical acceptability threshold (33%). In an independent validation cohort of 60 patients, 3.5/6SH maintained a small bias (median deviation -1.29 mL; percentage deviation -1.27%) and excellent agreement with 3D Slicer (ICC = 0.979). Inter- and intrarater ICCs for 3.5/6SH measurements in the validation cohort were 0.994 and 0.998, respectively, supporting excellent reproducibility. The average calculation time was 77.95 sec for 3.5/6SH-longer than for 1/2ABC (35.95 sec), but substantially shorter than for 3D Slicer (19.04 min). The 3.5/6SH formula showed high accuracy and agreement with 3D Slicer across all metrics and offers a reliable, simplified method for bedside cSDH volume estimation that may facilitate more consistent volume assessment in multicenter research and clinical practice, particularly for more sensitive monitoring of hematoma changes in resource-limited environments.
MEG Working Memory N-Back Task Revealed Functional Deficits in Children with Mild Traumatic Brain Injury.
Huang MX, Angeles-Quinto A, Robb-Swan A … +9 more , Bigler ED, Wilde EA, Vaida F, Troyer EA, Hesselink JR, Cheng CK, Meng W, Zimmerman E, Max JE
J Neurotrauma · 2026 May · PMID 42138124 · Publisher ↗
Mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive complaints in children. However, the TBI-related mechanisms underlying persistent cognitive symptoms including working memory (WM) dysfunction...
Mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive complaints in children. However, the TBI-related mechanisms underlying persistent cognitive symptoms including working memory (WM) dysfunction are not fully understood. Few pediatric studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in children with mTBI within a 3-week post-injury period. Children aged 8-15 years with mTBI ( = 60) and orthopedic injury (OI) controls ( = 37) from consecutive admissions to an emergency department were studied prospectively. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), theta (4-7 Hz), and delta (1-4 Hz) frequency bands. Compared with OI controls, children with mTBI showed decreased MEG signals (hypoactivity) across frequency bands in the proper WM network including dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex, and supramarginal gyrus (SMG), but over-recruitment with increased MEG signals (hyperactivity) in the frontal pole and ventromedial prefrontal cortex. The MEG activity from dlPFC and SMG regions also correlated with changes in symptom scores between 3-week and 3-month behavioral exams. This is the first pediatric study showing MEG hypoactivity from the WM proper network and over recruitment outside the WM network. One mechanism that may explain these novel findings could be the gamma-aminobutyric acid (GABA)-ergic inhibitory interneuron injury, which may cause disinhibition in the WM neural network, directly eliminating synchronized signals that are normally evoked by stimuli. This MEG study of abnormal MEG responses evoked by WM N-back stimuli provides a new functional imaging marker for pediatric mTBI.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe