J. Neurotrauma [JOURNAL]
Sun
200 papers
Examining Motor Unit Properties of Upper Limb Muscles Near the Zone of Injury in Chronic Cervical Spinal Cord Injury.
Debenham MIB, Ogalo E, Wu H … +4 more , McNeil CJ, Dalton BH, Stashuk D, Berger MJ
J Neurotrauma · 2026 Mar · PMID 41882962 · Publisher ↗
Spinal cord injury (SCI) causes muscle weakness or paralysis, with functional deficits partly due to motor neuron damage near or below the injury level. Understanding how damage affects the morphology and function of mot...
Spinal cord injury (SCI) causes muscle weakness or paralysis, with functional deficits partly due to motor neuron damage near or below the injury level. Understanding how damage affects the morphology and function of motor neurons and the muscle fibers they innervate (i.e., motor units [MUs]) is important for characterizing motor pathophysiology. We assessed MU electrophysiological properties in muscles innervated near the injury zone (anconeus: C7; extensor indicis [EI]: C8-T1) in motor-incomplete cervical SCI and controls. The EI of 14 SCI participants (48.2 ± 14.6 years; 1 female; C2:1, C4:5, C5:6, C6:2) were compared with 14 controls (44.4 ± 15.9 years; 2 females), and the anconeus was sampled from 9 participants per group (SCI: 52.0 ± 15.8 years, 1 female; controls: 47.3 ± 17.4 years, 1 female). Participants completed multiple, 15-s low-intensity elbow (anconeus) and finger (EI) extensions to study MU potentials (MUPs) recorded using monopolar needle and surface electromyography (EMG). Automated signal-decomposition software provided quantitative data from needle-detected MUPs, surface-detected MUPs (S-MUPs), and near-fiber MUPs (NFMs). The anconeus had fewer MUP phases and turns (≥11%) in SCI than controls ( < 0.05), but MUP, S-MUP, and NFM parameters were not different ( ≥ 0.11). Conversely, multiple EI MUP, S-MUP, and NFM parameters were larger (≥23%) for SCI than controls ( < 0.05). Interestingly, the more caudally innervated EI demonstrated MU adaptations indicative of chronic denervation, while the more rostrally innervated anconeus did not. Thus, our findings indicate that MUs located in spinal segments farther from the injury may be more susceptible to transsynaptic degeneration than MUs located closer to the injury site.
The Sunny Side Up.
Su Z
J Neurotrauma · 2026 Mar · PMID 41882961 · Publisher ↗
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Wearable Tracking of Eye and Body Movements During Breaching Training: Toward Real-Time Blast Injury Monitoring.
Kemmerer JP, Williamson JR, Kim J … +3 more , Halford E, Rao HM, Smalt CJ
J Neurotrauma · 2026 Mar · PMID 41882958 · Publisher ↗
Repeated exposure to blast overpressure in occupational settings has been associated with changes in cognitive and psychological health, as well as deficits in neurosensory subsystems. In this work, we describe a wearabl...
Repeated exposure to blast overpressure in occupational settings has been associated with changes in cognitive and psychological health, as well as deficits in neurosensory subsystems. In this work, we describe a wearable system to simultaneously monitor physiology and blast exposure levels and demonstrate how this system can identify individualized exposure levels corresponding to acute physiological response to blast exposure. Machine learning was used to develop a dose-response model that fused multiple physiological measures (electrooculuography, gait, and balance) into a single risk score by predicting the level of blast exposure on held-out subjects (Fused model, = 0.60). For our system, cohort, and environment, we found that blast events with peak pressure levels as low as 0.3 pound per square inch (PSI) could be related to physiological changes with blast exposure. We also identified an individual subject with longitudinally increasing reaction time scores who consistently showed a rapid and anomalous change in physiology-based risk scores after exposure to low-level blast events. Our results suggest that wearable technology may be viable for measuring physiological changes that are related to occupational blast exposure. Ultimately, this approach might be used to prevent neurotrauma from repeated exposure and to help set limits for a population or on an individual basis.
Subconcussive Preconditioning Modifies Acute Microglial Response and Improves Cognitive Outcomes Post-Concussion.
Anderson ED, Kim K, Georges AP … +4 more , Naveen A, Grajales E, Augustin DV, Meaney DF
J Neurotrauma · 2026 Mar · PMID 41882520 · Publisher ↗
Subconcussive impacts are highly prevalent in contact sports and are thought to increase concussion risk. However, the specific conditions under which these subconcussive impacts influence concussion outcomes are uncerta...
Subconcussive impacts are highly prevalent in contact sports and are thought to increase concussion risk. However, the specific conditions under which these subconcussive impacts influence concussion outcomes are uncertain, limiting our understanding of the mechanisms behind repetitive head trauma. Given that subconcussive impacts elicit a microglial response, we examined how subconcussive preconditioning affects microglial morphology and transcriptomic profile, as well as cognitive outcome after concussion. To investigate this question, we developed and validated a scalable, closed-head controlled cortical impact model. Using this approach, we found that although concussion elicited morphological features of hyper-surveillant microglia at 1 day post-injury, they resolved by 9 days post-injury, and subconcussive impacts only produced microglial changes at 9 days post-injury. When subconcussive impacts preceded a concussive impact (i.e., preconditioned concussion), no changes in microglial morphology appeared at either 1 day or 9 days after injury. Subconcussive preconditioning also upregulated microglial genes associated with inhibiting pro-inflammatory pathways and enhancing folate metabolism. Interestingly, subconcussive preconditioning eliminated concussion-associated cognitive deficits in novel object recognition and this cognitive protection was time dependent: preconditioning impacts were only protective if delivered within 2 min of concussion and had no effect if delivered over a 48-h window. These results suggest that some types of subconcussive impacts may offer protection against subsequent concussion and mitigate changes in microglial morphology and inflammatory responses. Understanding this timing window could inform strategies for minimizing cognitive impairments in athletes exposed to repetitive head trauma.
The Effect of Mild Traumatic Brain Injury on the Hypothalamic-Pituitary-Ovarian Axis: A Narrative Review.
Opene BN, Zynda AJ, Snook M … +6 more , Zeleznik A, Walker W, Elbin RJ, Anto-Ocrah M, Kontos AP, Rios JM
J Neurotrauma · 2026 Mar · PMID 41882512 · Publisher ↗
Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury (TBI), with 2.5 million cases reported annually in the United States. mTBI involves diverse signs, symptoms, and functional impairments...
Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury (TBI), with 2.5 million cases reported annually in the United States. mTBI involves diverse signs, symptoms, and functional impairments that typically resolve within 1 month, but may persist. Female sex is one of the most consistent predictors associated with an increased risk of mTBI and worse outcomes, including greater symptom severity and prolonged recovery. Emerging evidence also suggests that females are at greater risk of menstrual cycle dysfunction following mTBI, which could have downstream consequences on reproductive and related women's health outcomes. Researchers have speculated that the underlying mechanism for these detrimental effects is the injury's impact on the hypothalamic-pituitary-ovarian (HPO) axis; however, it is necessary to further clarify the extent of these disruptions, identify consistent patterns across studies, and determine potential implications for reproductive health and hormonal regulation following mTBI. The goal of this narrative review is to understand the effects of mTBI on the HPO axis, identify gaps in the research and clinical practice, and provide recommendations to address these issues in females with mTBI. We summarize: (1) sex differences observed following mTBI, including physiological variables that contribute to these differences, particularly the menstrual and ovulatory cycles in females; (2) pituitary gland functions and hormonal regulations; (3) pituitary and hormonal dysfunction after mTBI; and (4) implications of hormone dysregulation on mTBI recovery. Our review concludes by highlighting methodological gaps, research needs, strategy recommendations, and treatment referrals for patients with HPO axis dysfunction after mTBI.
Preconditioning Effect of Hydrogen Gas on Traumatic Brain Injury.
Nakagawa M, Tomura S, Toyooka T … +3 more , Fujii K, Tomiyama A, Wada K
J Neurotrauma · 2026 Mar · PMID 41877520 · Publisher ↗
Traumatic brain injury (TBI) affects approximately 1% of the global population annually. In Japan, sports-related head injuries are recognized as one of the most common causes. There have been reports suggesting that TBI...
Traumatic brain injury (TBI) affects approximately 1% of the global population annually. In Japan, sports-related head injuries are recognized as one of the most common causes. There have been reports suggesting that TBI sustained during sports activities may become more severe because of the added oxidative stress compared with injuries at rest, but there are still few reports on the actual changes in oxidative stress following TBI. Therefore, we first examined the changes in oxidative stress immediately post-sports-related TBI. No pharmacological treatment has been established to effectively prevent TBI, and preconditioning approaches aimed at enhancing endogenous tolerance prior to injury have attracted attention. However, existing methods often involve invasive procedures, limiting their clinical applicability. Prior studies demonstrated the therapeutic potential of hydrogen gas, which possesses antioxidant properties in TBI. Therefore, we examined whether hydrogen administration prior to TBI could attenuate secondary brain injury in a model incorporating exercise-induced oxidative stress before trauma. Male C57BL/6 mice (6 weeks old) were subjected to treadmill exercise at 15 m/min for 90 min to induce oxidative stress. During exercise, 1.3% hydrogen gas was delivered into the chamber for preconditioning. Moderate TBI was induced using a controlled cortical impact (CCI) device immediately postexercise. Four groups were evaluated: resting controls, exercise alone, exercise followed by TBI induced by CCI (ExCCI), and hydrogen-preconditioned exercise followed by TBI. Oxidative stress was assessed using hippocampal malondialdehyde (MDA) levels, and antioxidant capacity was evaluated using manganese superoxide dismutase (MnSOD) activity. Brain edema was quantified using brain water content, and vasogenic edema was assessed using Evans Blue extravasation. Histological analysis of the pericontusional cortex included glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) immunofluorescence. MDA levels increased 3 h postexercise and remained elevated for 24 h when TBI was induced. Hydrogen preconditioning significantly reduced MDA levels and enhanced MnSOD activity, which peaked 24 h postinjury. At the same time point, ExCCI mice showed significant brain and vasogenic edema, both of which were attenuated by hydrogen. GFAP and AQP4 were increased in ExCCI mice and suppressed by hydrogen. Although hydrogen is known to disappear from the blood within approximately 1 h postinhalation, MnSOD activity remained elevated for up to 24 h postinjury, indicating endogenous antioxidant defense activation. Hydrogen is considered to mitigate blood-brain barrier vulnerability to oxidative stress, thereby reducing vasogenic edema. These findings indicate that hydrogen gas may be effective as a treatment and a preventive intervention for TBI.
Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.
Ferede Z, Patterson S, Perera J … +3 more , Barker N, Cramb S, Flaws D
J Neurotrauma · 2026 Mar · PMID 41873521 · Publisher ↗
Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resource...
Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resources limit routine monitoring of all patients, trauma care remains largely symptom-driven. The combination of long-term disability and limited capacity for routine follow-up highlights the need for risk-stratified follow-up care and reliable evidence on early prognostic factors. However, the existing literature is sparse and methodologically heterogeneous, limiting the clinical applicability of findings. We therefore conducted a systematic review and meta-analysis to identify early risk factors for poorer long-term mental health and HRQoL outcomes. A systematic search of seven electronic databases identified studies of adult patients with TBI, with outcomes assessed at least 6 months postdischarge. Two authors independently screened the studies, assessed the risk of bias, and extracted the data. We pooled effect estimates using a random-effects meta-analysis and calculated 95% prediction intervals. A narrative synthesis was applied when meta-analysis was not feasible. The review was registered with PROSPERO (CRD42024576912) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 8,104 articles screened, 64 studies met the inclusion criteria ( = 334,672). Most studies (58%) had a low risk of bias. Female sex, socioeconomic disadvantage, psychiatric history, assaultive-related injuries, and previous TBI were consistently associated with worse long-term outcomes. Across meta-analyses, assault-related injuries more than doubled the odds of post-traumatic stress disorder (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 2.01-3.66, 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, 98%) were associated with higher odds of depression. Furthermore, higher pooled anxiety scores were observed in females and in individuals with a psychiatric history. The study identified several readily available factors present before or at discharge that are associated with poor long-term HRQoL and mental health outcomes. Leveraging these factors in follow-up protocols, prediction modeling, and clinical decision support systems may facilitate risk-stratified postdischarge care for TBI patients.
Spinal Cord Perfusion Pressure Monitoring after Traumatic Spinal Cord Injury: Indications, Techniques, and Future Horizons.
Tang-Tan A, Caldwell DJ, Aabedi AA … +4 more , Velasco MC, Manley GT, Tarapore PE, Yue JK
J Neurotrauma · 2026 Mar · PMID 41873454 · Publisher ↗
Impaired spinal cord perfusion can negatively impact neurological outcome after acute traumatic spinal cord injury (SCI). Hemodynamic management emphasizes maintenance of mean arterial pressure (MAP), although clinical p...
Impaired spinal cord perfusion can negatively impact neurological outcome after acute traumatic spinal cord injury (SCI). Hemodynamic management emphasizes maintenance of mean arterial pressure (MAP), although clinical practice remains variable and may be driven by systemic perfusion goals. Growing evidence suggests that spinal cord perfusion pressure (SCPP)-defined as MAP minus intrathecal pressure (ITP) measured via lumbar cerebrospinal fluid (CSF) or intraspinal pressure (ISP) measured directly at the injury site-may be a more meaningful physiological target. This narrative review synthesizes current SCPP monitoring techniques, emphasizing technical considerations for device placement, safety profiles, practical clinical factors guiding patient selection, and key gaps in current guidelines. A targeted literature search was performed using PubMed and Ovid MEDLINE for studies examining SCPP, ITP, CSF drainage, and hemodynamic management in traumatic SCI. Additional sources were identified through reference screening of key articles and prior reviews. Intrathecal lumbar subarachnoid drains (LSADs) are widely accessible, allow estimation of ITP, and facilitate CSF drainage, but have uncertain accuracy in the setting of spinal cord swelling and restricted CSF flow. LSADs advanced toward the site of injury offer the potential for local ITP assessment, although data remain sparse. ISP monitors provide high-fidelity measurements at the lesion site but cannot drain CSF, require intraoperative placement, and lack regulatory approval. Across modalities, key unresolved questions include optimal timing of monitor insertion, target SCPP ranges, and appropriate duration of monitoring. SCPP monitoring holds promise for individualizing hemodynamic management in acute traumatic SCI. Although studies suggest feasibility and potential benefit, consensus multi-institutional standardized guidelines are lacking. Future multicenter trials are needed to define indications, refine perfusion targets, and integrate SCPP-directed therapy into routine SCI care.
CT-Based Automated Segmentation and Recurrence Prediction in Chronic Subdural Hematoma: A Dual-Label Multicenter Study.
Wu H, Lv X, Yang J … +15 more , Lei D, Wan S, Bai C, Zhuang S, Wang B, Wei D, Long X, Xue H, Zhang X, Fan X, Huang L, Tian Z, Li M, Wang H, Yin X
J Neurotrauma · 2026 Mar · PMID 41873452 · Publisher ↗
Chronic subdural hematoma (CSDH) frequently recurs after burr-hole surgery, yet most prior imaging studies have focused primarily on hematoma and have not addressed the biomechanical effects of brain compression, which m...
Chronic subdural hematoma (CSDH) frequently recurs after burr-hole surgery, yet most prior imaging studies have focused primarily on hematoma and have not addressed the biomechanical effects of brain compression, which may play an important role in recurrence. In addition, reliance on manual annotation and subjective feature selection limits reproducibility and hinders large-scale clinical translation. This multicenter study included 897 patients with CSDH from six medical centers and developed a fully automated dual-label framework, termed CSDH-Net, to simultaneously segment CSDH and compressed brain tissue using nnU-Net, characterize their interaction through radiomic, volumetric, topological, and intensity-based features, and provide objective recurrence prediction. Recurrence risk was modeled using LightGBM with cross-validation and externally validated in two independent centers, and model interpretability was assessed through shapley additive explanations (SHAP) analyses. The segmentation model achieved a Dice score of 0.953 in internal validation and scores of 0.875 (for CSDH) and 0.980 (for compressed brain tissue) in external testing. The recurrence prediction model yielded area under the receiver operating characteristic curves of 0.830 in training and 0.741 in external validation. At a clinically justified threshold prioritizing sensitivity, the model achieved 85% recall in the external test cohort with acceptable specificity. SHAP and feature importance analyses consistently identified gray-level dependence nonuniformity, hematoma surface area/axis length, mean curvature of compressed brain tissue, and a cross-label spatial descriptor reflecting hematoma thickness as biologically meaningful predictors across datasets. These findings demonstrate that CSDH-Net enables accurate dual-label segmentation and interpretable, imaging-based recurrence prediction across different centers, offering objective and reproducible risk stratification that may support preoperative counseling, personalized follow-up planning, and integration into routine neurosurgical workflows. This study was prospectively registered in the Chinese Clinical Trial Registry (ChiCTR2500110736).
Prolonged Repetitive Trans-Spinal Magnetic Stimulation Promotes Superior Functional Recovery After Severe Spinal Cord Injury in Rats.
Garrido E, Robac A, Hugede A … +5 more , Neveu P, Delarue Q, Marie JP, Derrey S, Guérout N
J Neurotrauma · 2026 Mar · PMID 41870033 · Publisher ↗
Spinal cord injury (SCI) results in permanent disability in affected individuals. Immediately after SCI, a cascade of cellular and molecular events leads to the formation of a spinal scar. To date, no curative treatment...
Spinal cord injury (SCI) results in permanent disability in affected individuals. Immediately after SCI, a cascade of cellular and molecular events leads to the formation of a spinal scar. To date, no curative treatment is available for paraplegic or tetraplegic patients, underscoring the urgent need for pre-clinical research into innovative therapeutic strategies. Our laboratory has recently demonstrated that the spinal scar can be noninvasively modulated using repetitive trans-spinal magnetic stimulation (rTSMS). In both rat and mouse models, we showed that rTSMS applied for 14 consecutive days starting the day after injury modulates the lesion environment and promotes functional recovery. However, in rats with severe SCI, the effects on locomotion remain moderate. In this study, to move closer to potential clinical translation, we investigated whether extending rTSMS to 28 consecutive days could enhance recovery in a rat model of complete spinal cord transection. Based on detailed behavioral assessments, our results confirm that rTSMS improves locomotor recovery following severe SCI. These functional improvements are supported by immunohistochemical analyses of the lesion site. Notably, the beneficial effects of rTSMS appear to be maximized with 28 days of stimulation, with no observable adverse effects. This study provides further evidence that long-term rTSMS is a promising and safe approach, bringing us a step closer to its future clinical application in humans.
Blood Biomarkers for Identifying Epidural Hematoma in Patients Presenting with a Glasgow Coma Scale of 13-15: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.
Malmi K, Pisică D, Hossain I … +16 more , Mohammadian M, van Essen T, Luoto TM, Mondello S, Takala RSK, Tenovuo O, Vande Vyvere T, Vreeburg R, Yue JK, Maas AIR, Wang KKW, Menon DK, Newcombe VFJ, Büki A, Posti JP, CENTER-TBI Investigators and Participants
J Neurotrauma · 2026 Mar · PMID 41870014 · Publisher ↗
Triage of patients with mild traumatic brain injury (mTBI) and possible isolated epidural hematoma (iEDH) remains a clinical challenge. Blood-based biomarkers are being integrated into mTBI management, but their ability...
Triage of patients with mild traumatic brain injury (mTBI) and possible isolated epidural hematoma (iEDH) remains a clinical challenge. Blood-based biomarkers are being integrated into mTBI management, but their ability to identify patients with iEDH is uncertain. In this prospective, multicenter cohort study from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study, which recruited between December 19, 2014, and December 17, 2017 (NCT02210221), we included 1,048 mTBI patients (Glasgow Coma Scale ≥ 13) with biomarker sampling and head computed tomography (CT) within 24 h of injury. We assessed six blood-based biomarkers-including glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)-for their diagnostic performance in identifying patients with mTBI and iEDH. Patients with other traumatic intracranial findings potentially requiring surgery were excluded. Of 1,048 patients (median age 46 years; 64% male), 38 (3.6%) had iEDH and 982 (94%) had negative CT findings. GFAP showed the highest diagnostic accuracy for iEDH (area under the curve 0.77; 95% confidence interval 0.71-0.83) and yielded a negative predictive value of 1.0 at a threshold of 0.19 μg/L. The addition of UCH-L1 did not lead to a significant improvement in diagnostic performance. No significant correlation was found between EDH volume and biomarker levels. In this large multicenter study, GFAP was the only biomarker that could adequately distinguish patients with iEDH from CT-negative cases. These results suggest that GFAP may serve as a tool to rule out iEDH in patients with Glasgow Coma Scale ≥ 13, supporting its use in identifying individuals unlikely to require acute intervention for intracranial injury.
Low or Low-Normal Insulin-Like Growth Factor 1 After Traumatic Brain Injury: Interpretation and Implications.
Mishra V, Martinez M, Weppner J
J Neurotrauma · 2026 Mar · PMID 41866985 · Publisher ↗
Growth hormone deficiency (GHD) is a prevalent consequence of traumatic brain injury (TBI) that can contribute to prolonged adverse symptoms and impaired quality of life. The overlap between symptoms of GHD and chronic T...
Growth hormone deficiency (GHD) is a prevalent consequence of traumatic brain injury (TBI) that can contribute to prolonged adverse symptoms and impaired quality of life. The overlap between symptoms of GHD and chronic TBI complicates the clinical picture, highlighting the need for precise diagnostic tools. Insulin-like growth factor 1 (IGF-1), a key mediator of growth hormone (GH) activity, is frequently utilized as a surrogate marker of GH status. However, IGF-1 levels may be normal in patients with confirmed GHD. Furthermore, low or low-normal IGF-1 is not specific to GHD, and provocative testing is required to confirm GHD in most patients with suspected deficiency. To provide a pragmatic clinical framework for interpreting IGF-1 -score <0 in symptomatic patients after TBI, we reviewed the literature in the PubMed and PubMed Central databases addressing IGF-1 and GHD, differential diagnoses associated with low and low-normal IGF-1, and international guidelines on GH testing. Among TBI patients, GHD remains a leading cause of reduced IGF-1, but alternative diagnoses include malnutrition, chronic liver or kidney disease, poorly controlled diabetes mellitus, hypothyroidism, sepsis, and genetic conditions such as Laron syndrome. A systematic and evidence-based approach to IGF-1 interpretation is essential for distinguishing primary neuroendocrine dysfunction from secondary causes. The use of -scores improves diagnostic precision by standardizing IGF-1 levels for age and sex. Our framework aids clinicians in integrating thorough neuroendocrine evaluation with broader medical assessments, clinical considerations, and comorbidities, thereby improving diagnostic accuracy and patient management. Future research should emphasize refined screening protocols for neuroendocrine dysfunction in TBI.
Utility of Amyloid Beta and Tau Positron Emission Tomography Scans for Identifying Early-Stage Neurodegenerative Changes in Former Professional Football Players and Healthy Controls: Results from the Brain Health Initiative.
Eagle SR, Collins M, Kontos AP … +14 more , Lopez O, Mountz JM, Wisniewski SR, Edelman K, Benso S, Beers S, Soose RJ, Puccio A, Rosario B, Laymon CM, Lopresti B, Minhas D, Agarwal V, Okonkwo DO
J Neurotrauma · 2026 Mar · PMID 41854183 · Publisher ↗
The aim of this study is to determine if there is a difference in tau and amyloid beta (Aβ) deposition on positron emission tomography (PET) scans between former players and controls, and if there is a differential assoc...
The aim of this study is to determine if there is a difference in tau and amyloid beta (Aβ) deposition on positron emission tomography (PET) scans between former players and controls, and if there is a differential association of the tau and Aβ deposition with concussion symptom burden. Participants completed the Rivermead Post-Concussion Questionnaire (RPQ) and PET imaging using Pittsburgh Compound B (PiB) and AV1451 ligands to identify uptake of Aβ and tau, respectively. Aβ standardized uptake value ratios (SUVR) and tau SUVR were compared between players and controls using a general linear model including age, race/ethnicity, years of education completed, and total number of prior sport-related traumatic brain injuries (TBIs) as covariates. A series of linear regression models were built to predict RPQ symptom scores including group status (player vs. control), Aβ SUVR and tau SUVR, and the interaction between group status and the Aβ SUVR and tau SUVR. Former players reported 4.9 ± 2.8 and control reported 1.4 ± 1.6 prior sport-related TBIs. Neither group reported any non-sport-related TBIs. Former players had higher RPQ symptom scores (13.3 ± 1.8) compared with controls (4.7 ± 1.8; = 0.003). Controls had higher uptake for Aβ in the precuneus (1.22 ± 0.02) compared to players (1.14 ± 0.02; corrected = 0.007). There were no differences between groups in uptake for Aβ in any other region of interest or tau in any region of interest. None of the regression models associating the interaction of group status and uptake with RPQ symptoms were significant. Aβ and tau PET scans may have limited utility for identifying potential neuropathological differences between participants with a career in professional football from controls who did not play football beyond high school. The PET tracer used for tau in the current study (AV1451) is well-suited for Alzheimer's disease-related tau pathology with limited binding for chronic traumatic encephalopathy-type tau proteins. A PET tracer for chronic traumatic encephalopathy-related tau deposition should remain a focus of future research.
Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI Study.
Nelson LD, Simons MU, Jain S … +8 more , Sun X, Choi K, Temkin N, Diaz-Arrastia R, Gardner R, Taylor S, Manley GT, Stein MB
J Neurotrauma · 2026 Mar · PMID 41852022 · Full text
Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and execut...
Patients with traumatic brain injury (TBI) and Glasgow Coma Scale scores of 13-15 (historically called mild TBI [mTBI]) commonly experience changes in cognitive functioning, including processing speed, memory, and executive functioning. In a prospective sample ( = 523) of individuals of European descent who had been treated in a U.S. level 1 trauma center for mTBI, we examined the prognostic value of four polygenic risk scores (PRS) for cognitive outcomes at 6-months postinjury. To estimate the impact of mTBI on cognition, primary cognitive outcomes were scaled as -scores reflecting changes in performance relative to predicted preinjury performance. The PRS examined were previously developed and validated to predict cognition-related outcomes of educational attainment (Education-PRS), intelligence (Intelligence-PRS), and Alzheimer's disease (AD-mild traumatic brain injury (APOE)-PRS and AD + APOE-PRS). Both the Education-PRS and Intelligence-PRS displayed bivariate associations with all four cognitive outcomes (β = 0.19-0.32), whereas neither Alzheimer's disease PRS was significantly associated with any outcome. After controlling for other factors known to predict cognitive outcomes of TBI (e.g., sex, education, mTBI severity defined by a combination of Glasgow Coma Scale scores and the presence/absence of acute intracranial findings on clinical neuroimaging), the Education-PRS and Intelligence-PRS remained independently predictive of verbal episodic memory (β = 0.10-0.16), whereas their associations with processing speed and executive functioning were mostly nonsignificant and were mediated through educational attainment. Looking across primary -score and secondary raw score outcomes, cognitive outcomes 6 months post-mTBI were good on average, and PRS made small independent contributions to outcome prediction. The mediation model findings may support theories of cognitive reserve, which propose that individuals with stronger preinjury cognitive processing abilities (often estimated by educational history) can better compensate for TBI. Moreover, findings indicate that PRS may contribute modestly to multivariable models predicting cognitive function after TBI.
Comparing Direct and Indirect Transfer Pathways for Pediatric Traumatic Brain Injury: Insights from a UK Specialist Neuroscience Center.
Adidharma P, Allison CM, Giannakaki V … +3 more , Jayakumar N, Coulter IC, Cowie CJA
J Neurotrauma · 2026 Mar · PMID 41852019 · Publisher ↗
Optimal transfer strategies for pediatric traumatic brain injury remain debated: direct transfer to a specialist neuroscience center expedites access to neurosurgical care, whereas indirect transfer via a trauma unit all...
Optimal transfer strategies for pediatric traumatic brain injury remain debated: direct transfer to a specialist neuroscience center expedites access to neurosurgical care, whereas indirect transfer via a trauma unit allows initial stabilization before secondary transfer. We retrospectively analyzed 375 pediatric traumatic brain injury admissions managed under United Kingdom national guidelines (2019-2024): 184 (49%) were transferred directly to a specialist neuroscience center and 191 (51%) were initially transported to a trauma unit before secondary transfer. Outcomes were assessed using the Pediatric Glasgow Outcome Scale-Extended. The primary outcome was good recovery (upper or lower good); secondary outcomes were time to neurosurgical care, length of stay, complications, and mortality. Propensity score matching and generalized linear models were used to adjust for confounding, with a sensitivity analysis including patients with more than 30 days of follow-up. Protocol fidelity for triage to direct or indirect transfer was 95.2%. Before matching, patients in the direct transfer group were older and had more severe clinical features. In the matched cohort (156 direct, 176 indirect), 81.6% were managed conservatively. Although not statistically significant, follow-up duration was longer in the direct transfer group. Good recovery occurred in 79% of the direct group and 80% of the indirect group, with no significant association between transfer pathway and good recovery (adjusted odds ratio 1.02, 95% confidence interval 0.57-1.86). Times from injury to CT scan, neurosurgical referral, and neurosurgical intervention were significantly shorter in the direct transfer group (all < 0.05). No between-group differences were observed in length of stay, inpatient or long-term complications, or mortality. The sensitivity analysis yielded concordant findings. Direct transfer shortened the time to neurosurgical care, but within the detectable effect size of this study, no pathway-related difference in clinical outcomes was demonstrated.
Efficacy of Minocycline in Acute Traumatic Spinal Cord Injury.
Omair J, Sheth A, Elsamadicy AA … +7 more , Rahmani R, Freeman D, Williams B, Sieg E, Altstadt T, Boakye M, Dietz N
J Neurotrauma · 2026 Mar · PMID 41851023 · Publisher ↗
Traumatic spinal cord injury (SCI) leads to irreversible neurological deficits, and no acute pharmacologic therapy has demonstrated consistent benefit. Minocycline, a tetracycline antibiotic with anti-inflammatory and ne...
Traumatic spinal cord injury (SCI) leads to irreversible neurological deficits, and no acute pharmacologic therapy has demonstrated consistent benefit. Minocycline, a tetracycline antibiotic with anti-inflammatory and neuroprotective properties, has been proposed as a therapeutic candidate. We performed a PRISMA-guided systematic review of PubMed and Embase (January 2000-July 2024) to evaluate minocycline in acute SCI. Twenty-six studies met the inclusion criteria, comprising three human trials and 23 animal studies. In humans, intravenous minocycline (200-400 mg daily for 7 days) achieved cerebrospinal fluid concentrations of ∼2.3 µg/mL, below the therapeutic range suggested by preclinical models (35-75 µg/mL). Cervical SCI patients showed numerically greater motor recovery (+14 American Spinal Cord Injury Association motor points vs. controls), but findings were underpowered and did not consistently reach significance. Biomarker modulation, including reduced HO-1 and NfL levels, suggested biological activity yet failed to translate into functional improvement. Animal studies demonstrated consistent benefits, with higher Basso, Beattie, and Bresnahan locomotor scores (14.6 ± 0.6 vs. 8.3 ± 0.7 at 28 days, < 0.001), reduced lesion volume by up to 58%, preserved white matter, and attenuation of inflammatory, apoptotic, and oxidative cascades in a dose- and route-dependent manner. Overall, minocycline exerts robust neuroprotective effects in preclinical SCI but limited functional benefit in humans, largely due to subtherapeutic central nervous system penetration at tolerated systemic doses. Future trials should explore optimized delivery strategies, include demographic stratification, and employ standardized functional endpoints to better define translational potential.
A Multicenter Evaluation of Sex-Specific Differences in Pre-Hospital Care and Patient Outcome of Severe Traumatic Brain Injury: A Multicenter Cohort Study.
Mansvelder FJ, Beijer E, Schwarte LA … +12 more , Bulte CSE, Loer SA, Bloemers FW, Van Lieshout EMM, Hartog DD, Hoogerwerf N, van der Naalt J, Absalom AR, Eberl S, Bossers SM, Schober P, BRAIN-PROTECT collaborators
J Neurotrauma · 2026 Mar · PMID 41847837 · Publisher ↗
Severe traumatic brain injury (TBI) is a major cause of mortality and disability, with a higher incidence among males. Consequently, research has pre-dominantly focused on males, leaving sex-related disparities underexpl...
Severe traumatic brain injury (TBI) is a major cause of mortality and disability, with a higher incidence among males. Consequently, research has pre-dominantly focused on males, leaving sex-related disparities underexplored. This study investigates sex differences in outcomes after severe TBI. A retrospective analysis was conducted using data from the BRAIN-PROTECT study, a multicenter cohort of patients with severe TBI treated by Dutch Helicopter Emergency Medical Services. The primary outcome was 30-day mortality in females versus males. Patients were stratified by age (≤45 and >45 years), and logistic regression was used for analysis. In total, 1824 patients were eligible for data analysis. No significant sex differences in overall mortality at 30 days were found (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.98-1.46, = 0.084). However, when stratified by age, females aged ≤45 years showed significantly reduced mortality (OR 0.70, 95% CI 0.50-0.98, = 0.037) and better Glasgow Outcome Scale scores (OR 1.36, 95% CI 1.12-1.64, = 0.002) compared with males of the same age group. In this large multicenter cohort, the association between sex and 30-day mortality after severe TBI was age-dependent. Although younger females showed better unadjusted outcomes than males, this difference appeared to be largely explained by differences in injury severity and case-mix rather than sex alone.
Sex Differences in the Treatment Effect of Targeted Heart Rate Aerobic Exercise in Adolescents with Acute Sport-Related Concussion.
Castro EV, Chizuk HM, Leddy JJ … +3 more , Aronoff N, Valera EM, Haider MN
J Neurotrauma · 2026 Mar · PMID 41847834 · Publisher ↗
Prescribed aerobic exercise is the recommended treatment for athletes with sport-related concussion (SRC) who present with exercise intolerance. A recent randomized controlled trial (RCT) found that higher volumes of aer...
Prescribed aerobic exercise is the recommended treatment for athletes with sport-related concussion (SRC) who present with exercise intolerance. A recent randomized controlled trial (RCT) found that higher volumes of aerobic exercise, compared with lower volumes, may not be as efficacious in adolescent females with SRC compared with adolescent males. We reanalyzed data from our previously published randomized controlled trials (RCT) and hypothesized that prescribed aerobic exercise, and not stretching, within 10 days of injury would result in faster recovery after SRC in males compared with females. The first RCT ( = 103) recruited from 2015 to 2018 and the second RCT ( = 115) recruited from 2018 to 2020. Sexes were compared in each RCT, then samples were stratified by sex, and intervention groups were compared using a Log-rank test. There were no significant differences in recovery times between males and females in either RCT, regardless of intervention. When stratified by sex and comparing intervention groups, males in RCT1 who were prescribed aerobic exercise ( = 28) recovered 6 days faster than males prescribed stretching ( = 27, = 0.004) but there was no significant difference for females (aerobic exercise [ = 24] vs. stretching [ = 24, 3-day difference, = 0.564]). In RCT2, males prescribed aerobic exercise ( = 39) recovered 8 days faster than the stretching group ( = 34, = 0.020), whereas there was no significant difference for females (aerobic exercise [ = 22] vs. stretching [ = 20, 3-day difference, = 0.587]). This reanalysis of prior RCT data revealed that male adolescents after SRC recovered significantly faster by 7-8 days when prescribed aerobic exercise within 10 days of injury, whereas female adolescents had a nonsignificant improvement of 3 days. Future adequately powered studies should account for variability between sexes.
Mild Traumatic Brain Injury Alters Hippocampal Sharp-Wave Ripple Properties: Implications in Memory Impairments.
Noble B, Homma R, Broussard JI … +3 more , Robinson D, Moore AN, Dash PK
J Neurotrauma · 2026 Mar · PMID 41847818 · Publisher ↗
A large body of evidence has shown that sharp wave ripples (SWRs), highly synchronized oscillations of the local field potential (LFP) in the CA1 pyramidal layer of the hippocampus, play a prominent role in memory consol...
A large body of evidence has shown that sharp wave ripples (SWRs), highly synchronized oscillations of the local field potential (LFP) in the CA1 pyramidal layer of the hippocampus, play a prominent role in memory consolidation. SWRs typically occur in periods of non-REM sleep, but have also been observed during awake rest periods of animals engaged in cognitive tasks. These events have been observed in rodents, non-human primates, and humans, suggesting they are evolutionarily conserved and contribute to memory formation. Numerous neurological diseases and insults, including traumatic brain injury (TBI), impair learning and memory. Mild TBI (mTBI) is the most prevalent form of TBI, and can cause memory impairments that, in some cases, last for months-to-years. Clinical and experimental studies have shown that these impairments can occur in the absence of visible physical damage to the hippocampus. In the present study, we examined whether an mTBI alters the properties of SWRs in rodents. Seven days after a mild fluid percussion injury (mFPI), recording electrodes were implanted into the CA1 subfield of the hippocampus of sham and injured rats. After seven days of recovery, LFPs and the activity of CA1 neurons were simultaneously recorded. Recordings were carried out when animals were exploring an arena containing two objects, one of which was moved between recording sessions. This allowed us to evaluate how changes in the environment affected SWR incidence and properties. Our data show that compared to uninjured controls, mFPI rats had reduced numbers of SWR events. Of the SWRs recorded, those from mTBI rats had shorter durations, reduced power, and higher frequencies than those in control animals. We also found that the modulation of the activity of CA1 pyramidal neurons by SWRs was markedly impaired in mTBI animals. Taken together, our data indicate that mTBI alters the electrophysiological properties of SWRs and reduces the synchronization of pyramidal neuron activity to SWRs. These electrophysiological changes may have implications in mTBI-associated memory impairments.
Repetitive Mild Traumatic Brain Injury Causes Neuronal Damage in the APP/PS1 Mouse Model of Alzheimer's Disease Without an Enduring Impact on Amyloid Pathology, Sleep, or Epileptiform Activity.
Yue J, Carriquiriborde V, Cheng WH … +6 more , Yildirim T, Fan J, Tok S, Kelly ML, Wellington CL, Kent BA
J Neurotrauma · 2026 Mar · PMID 41834411 · Publisher ↗
Traumatic brain injury (TBI) is a known risk factor for Alzheimer's disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the develop...
Traumatic brain injury (TBI) is a known risk factor for Alzheimer's disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimer's disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice ( = 19). One month post-injury, we implanted electroencephalogram and electromyographic electrodes, recorded for 72 h, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI 1 month post-injury; however, power spectra analysis showed a shift toward higher frequencies in the rmTBI group during non-rapid eye movement sleep. Epileptiform activity did not differ between sham and rmTBI. Compared with sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial fibrillary acidic protein in blood plasma and no change in Aβ pathology. These results indicate sustained neurological injury in the APP/PS1 mice 1 month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.
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