Journal of neurotrauma最新文献

{"title":"MEG Working Memory N-Back Task Revealed Functional Deficits in Children with Mild Traumatic Brain Injury.","authors":"Ming-Xiong Huang, Annemarie Angeles-Quinto, Ashley Robb-Swan, Erin D Bigler, Elisabeth A Wilde, Florin Vaida, Emily A Troyer, John R Hesselink, Chung-Kuan Cheng, Wenjing Meng, Elise Zimmerman, Jeffrey E Max","doi":"10.1177/08977151261433776","DOIUrl":"10.1177/08977151261433776","url":null,"abstract":"<p><p>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 (<i>n</i> = 60) and orthopedic injury (OI) controls (<i>n</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1569-1582"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948583","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":"Interferon-β Deficiency Selectively Modulates Chronic Microglial Pathways after Traumatic Brain Injury.","authors":"James P Barrett, Rebecca J Henry, Maria Vaida, Kari Ann Shirey, Stefanie N Vogel, Alan I Faden, Bogdan A Stoica","doi":"10.1177/08977151261434894","DOIUrl":"10.1177/08977151261434894","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) induces long-term, secondary injury processes that contribute to chronic neurodegeneration and associated neurological deficits. Previously, we demonstrated that controlled cortical impact in mice, a well-established experimental model of TBI, causes acute neuroinflammatory changes, including upregulation of interferon-β (IFN-β) and other type I interferon (IFN-I)-related genes in the injured cortex and hippocampus. Early inhibition of IFN-β signaling, either through intracerebroventricular administration of an anti-type I IFN receptor antibody or use of global IFN-β knockout mice (IFN-β^-/-), attenuates post-traumatic neuroinflammation and neurodegeneration and improves neurological outcomes for up to 28 days postinjury (dpi), with the knockout model showing more robust and sustained protective effects. However, the consequences of sustained suppression of these pathways after TBI have not been studied. Here, we examine the long-term effects of IFN-β deficiency on microglial activation, neuropathology, and neurological function during the chronic phase post-TBI (60-90 dpi). Transcriptomic analysis of isolated microglia from wild-type mice after TBI revealed persistent upregulation of IFN-I and other key neuroinflammatory genes, including classical pro-inflammatory and disease-associated microglia (DAM) at both 60 and 90 dpi. The IFN-I pathway was significantly attenuated in IFN-β^-/- mice at these later timepoints. However, IFN-β deficiency did not significantly alter the trauma-induced upregulation of DAM markers, indicating selectivity of chronic IFN-β modulation on injury-induced microglia-reactive phenotypes. Moreover, although IFN-β deficiency significantly attenuated pro-inflammatory phenotypes at 60 dpi, it enhanced the injury-mediated downregulation of homeostatic microglial genes at 90 dpi. In addition, no significant reduction in lesion volume or fine motor deficits was observed in IFN-β^-/- mice at chronic timepoints, although chronic post-traumatic cognitive impairment was attenuated. These findings suggest that global IFN-β deficiency has complex, time-dependent effects on chronic outcomes following TBI; although it improves cognitive function, it further suppresses homeostatic microglia that may partially limit long-term therapeutic benefits.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1681-1699"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581543","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":"A Multicenter Evaluation of Sex-Specific Differences in Pre-Hospital Care and Patient Outcome of Severe Traumatic Brain Injury: A Multicenter Cohort Study.","authors":"Floor J Mansvelder, Elise Beijer, Lothar A Schwarte, Carolien S E Bulte, Stephan A Loer, Frank W Bloemers, Esther M M Van Lieshout, Dennis Den Hartog, Nico Hoogerwerf, Joukje van der Naalt, Anthony R Absalom, Susanne Eberl, Sebastiaan M Bossers, Patrick Schober","doi":"10.1177/08977151261433821","DOIUrl":"10.1177/08977151261433821","url":null,"abstract":"<p><p>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, <i>p</i> = 0.084). However, when stratified by age, females aged ≤45 years showed significantly reduced mortality (OR 0.70, 95% CI 0.50-0.98, <i>p</i> = 0.037) and better Glasgow Outcome Scale scores (OR 1.36, 95% CI 1.12-1.64, <i>p</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1612-1622"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473870","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":"Comparing Direct and Indirect Transfer Pathways for Pediatric Traumatic Brain Injury: Insights from a UK Specialist Neuroscience Center.","authors":"Peter Adidharma, Callum M Allison, Venetia Giannakaki, Nithish Jayakumar, Ian C Coulter, Christopher J A Cowie","doi":"10.1177/08977151261433752","DOIUrl":"10.1177/08977151261433752","url":null,"abstract":"<p><p>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 <i>p</i> < 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1598-1611"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480969","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":"Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.","authors":"Zemedu Ferede, Sue Patterson, John Perera, Natalie Barker, Susanna Cramb, Dylan Flaws","doi":"10.1177/08977151261433824","DOIUrl":"10.1177/08977151261433824","url":null,"abstract":"<p><p>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 (<i>n</i> = 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, <i>I</i>² <i>=</i> 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, <i>I</i>² <i>=</i> 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, <i>I² =</i> 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, <i>I</i>² <i>=</i> 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, <i>I</i>² <i>=</i> 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, <i>I</i>² <i>=</i> 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, <i>I</i>² <i>=</i> 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1551-1568"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504109","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> 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":"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":"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}