Journal of neurotrauma最新文献

{"title":"Metabolomics in Mild Traumatic Brain Injury: A Scoping Review.","authors":"Labeeb Rashid, Eric Pimentel, Nadeem Bishtawi, Mohammad Mehdi Banoei, Chel Hee Lee, Brent W Winston","doi":"10.1177/08977151261492647","DOIUrl":"https://doi.org/10.1177/08977151261492647","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) accounts for around 80-90% of TBI cases, is increasing in incidence, and represents a major public health concern. Despite its high incidence, mTBI lacks reliable molecular biomarkers for diagnosis or prognosis. Metabolomics, the profiling of small-molecule metabolites (≤1 kDa), has emerged as a promising approach to characterize acute neurometabolic perturbations in mTBI and identify candidate biomarkers. However, metabolomic changes in mTBI have not yet been comprehensively characterized. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, we conducted a scoping review of studies from 2010 to 2025 on acute-phase (24-72 h post-injury) serum/plasma metabolomics in adult mTBI (Glasgow Coma Scale 13-15). Systematic searches of PubMed, Scopus, and Embase identified 11 eligible studies. Seven metabolites were consistently reported as altered in ≥2 studies: glucose and the ketone body 3-hydroxybutyrate were elevated in mTBI, whereas five amino acids (valine, isoleucine, glycine, methionine, and tryptophan) were decreased. Pathway analysis revealed branched-chain amino acid biosynthesis as the most enriched pathway, while one-carbon folate-mediated metabolism and energy metabolism were also implicated. Preliminary evidence indicates that acute mTBI also perturbs lipid metabolism, with increases in phospholipid breakdown products and sphingomyelins, reflecting membrane disruption and altered energy utilization. This metabolic signature aligns with known acute mTBI pathophysiology, including hypermetabolism, excitotoxicity, and neuroinflammation, and may reflect compensatory responses to increased energy demand and oxidative stress. These changes show promise as candidate biomarkers and therapeutic targets but require validation in larger cohorts to establish their utility in mTBI diagnosis, prognosis, and management.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261492647"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Mild Traumatic Brain Injury on the Hypothalamic-Pituitary-Ovarian Axis: A Narrative Review.","authors":"Belita N Opene, Aaron J Zynda, Meredith Snook, Anthony Zeleznik, William Walker, R J Elbin, Martina Anto-Ocrah, Anthony P Kontos, Julie M Rios","doi":"10.1177/08977151261433818","DOIUrl":"10.1177/08977151261433818","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1539-1550"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Polygenic Risk Scores in Predicting Cognitive Functioning after Mild Traumatic Brain Injury: A TRACK-TBI Study.","authors":"Lindsay D Nelson, Mary U Simons, Sonia Jain, Xiaoying Sun, Karmel Choi, Nancy Temkin, Ramon Diaz-Arrastia, Raquel Gardner, Sabrina Taylor, Geoffrey T Manley, Murray B Stein","doi":"10.1177/08977151261432398","DOIUrl":"10.1177/08977151261432398","url":null,"abstract":"<p><p>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 (<i>N</i> = 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 <i>z</i>-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 <i>z</i>-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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1589-1597"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> The Sunny Side Up.","authors":"Zhaohui Su","doi":"10.1177/08977151261433755","DOIUrl":"10.1177/08977151261433755","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"NP9-NP10"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Shawn R Eagle, Michael Collins, Anthony P Kontos, Oscar Lopez, James M Mountz, Stephen R Wisniewski, Kathryn Edelman, Steven Benso, Sue Beers, Ryan J Soose, Ava Puccio, Bedda Rosario, Charles M Laymon, Brian Lopresti, Davneet Minhas, Vikas Agarwal, David O Okonkwo","doi":"10.1177/08977151261433820","DOIUrl":"10.1177/08977151261433820","url":null,"abstract":"<p><p>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; <i>p</i> = 0.003). Controls had higher uptake for Aβ in the precuneus (1.22 ± 0.02) compared to players (1.14 ± 0.02; corrected <i>p</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1583-1588"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Residual Sedation in Patients with Traumatic Brain Injury after Cessation of Midazolam Infusion: Is There a Threshold Plasma Concentration?","authors":"Tim J L Smeets, Merle F de Lange, Birgit C P Koch, Diederik Gommers, Henrik Endeman, Nicole G M Hunfeld, Mathieu van der Jagt","doi":"10.1177/08977151261493435","DOIUrl":"https://doi.org/10.1177/08977151261493435","url":null,"abstract":"<p><p>In traumatic brain injury (TBI) patients, therapeutic drug monitoring of midazolam and its metabolites can help to assess residual sedation. Based on previous literature in non-TBI patients, it is assumed that concentrations of <100 ug/L of midazolam are non-sedative. The objective of this study was to assess the threshold sum concentration of midazolam and metabolites for residual sedation after cessation of midazolam infusion in critically ill TBI patients. We performed a retrospective study at the adult ICU of Erasmus University Medical Center between 07-2017 and 03-2024. TBI patients were included for analysis if sequential Glasgow Coma Scale (GCS) scores and at least one midazolam plasma concentration <100 ug/L was available. Residual sedation was evaluated based on improvement in the sum of the Eye and Motor scores from the GCS according to a decision rule. Among 51 patients, 75% (<i>n</i> = 38) had residual sedation. Median sum midazolam concentrations in the residual sedation versus no residual sedation group were 14 ug/L (3-32) and 7 ug/L (3-31), respectively. In the patients with residual sedation an improved EM score of 3 (2-5) was observed within 3 days (2-4) and 22 patients (58%) scored M6 within 4 (2-5) days. Finally, in the residual sedation and no residual sedation group we observed in hospital mortality rates of 5% and 46%, respectively. In TBI patients the threshold concentration for a residual sedative effect of midazolam appears to be much lower than previously described in non-TBI populations. Therefore, clinicians should be reluctant to make withdrawal or limitation of care decisions too early based on low GCS in TBI patients, even in the presence of very low plasma concentrations of midazolam and metabolites.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261493435"},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> Response to Cho et al.","authors":"Tong Sun, Junwen Guan","doi":"10.1177/08977151261486818","DOIUrl":"https://doi.org/10.1177/08977151261486818","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261486818"},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Response to Letter:</i> Regarding NEU-2025-0147.R2 Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries by Polina et al.","authors":"Gursimrat Bhatti, Meghan E Robinson, Taryn White, Ruosha Li, Melissa B Jones, Ricardo E Jorge","doi":"10.1177/08977151261490404","DOIUrl":"https://doi.org/10.1177/08977151261490404","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261490404"},"PeriodicalIF":3.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> Regarding Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries.","authors":"Polina Angelova, Dilyan Ferdinandov, Dimo Yankov, Ivo Kehayov","doi":"10.1177/08977151261490398","DOIUrl":"https://doi.org/10.1177/08977151261490398","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261490398"},"PeriodicalIF":3.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic Exercise Prevents the Loss of Endogenous Pain Modulation in Male and Female Rats with Traumatic Brain Injury.","authors":"Karen-Amanda Irvine, Adam R Ferguson, J David Clark","doi":"10.1177/08977151261483905","DOIUrl":"10.1177/08977151261483905","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) patients may suffer from several long-term complications after injury such as impaired motor skills, cognitive decline, and sensory abnormalities including chronic pain. Disruption of endogenous pain modulatory pathways likely contributes to the development of chronic pain in a wide range of conditions including TBI. Aerobic exercise has been shown to impact pain syndromes. Here, we investigate the effect of exercise on nociceptive outcome measures after TBI using a lateral fluid percussion (LFP) model and voluntary running wheels in male and female rats. We tested mechanical nociceptive reactivity with von Frey fibers and descending control of nociception (DCN) using hindpaw sensitization with prostaglandin E2 followed by a capsaicin-test stimulus to the forepaw. Pharmacological studies included administration of noradrenergic (NA) and serotoninergic receptor antagonists. Neuropathological studies quantified neuroinflammatory changes and axonal damage. We found that exercise decreased the duration of hindlimb hyperalgesia from ∼5 weeks to 2-3 weeks in female and male TBI rats, respectively. These gains were reversed by administration of the α₁-adrenoceptor (α₁-AR) antagonist, prazosin. Exercise also prevented the loss of DCN for at least 180 days post-injury in both male and female TBI rats. The intact DCN response in male and female TBI rats provided by exercise could be blocked using prazosin. Surprisingly, exercise-mediated restoration of the DCN response in male TBI rats was not blocked by the 5-HT₇ receptor antagonist, SB-267790, despite this being the receptor system through which serotonin reuptake inhibitors restore DCN after TBI in male rats. Assessment of neuropathology, conducted acutely after TBI, revealed that both astrocyte and microglial responses to injury were significantly greater in male TBI compared with female TBI rats, regardless of exercise. The effect of exercise on the extent of neuroinflammation after injury was minimal in TBI rats of both sexes. Exercise significantly reduced axonal loss in the corpus callosum in both male and female TBI rats compared with sedentary TBI rats. However, the extent of axonal loss after TBI in both exercise and sedentary male rats was greater than in female exercise and sedentary groups, respectively. These results demonstrate that exercise is a promising treatment for chronic nociception after TBI in both male and female rats. It also highlights that dysfunction of endogenous pain modulatory pathways in male TBI rats involving a transition from NA to serotonergic antinociception can be blocked by exercise, possibly by reducing axonal loss.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261483905"},"PeriodicalIF":3.8,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}