Journal of neurotrauma最新文献

{"title":"Expression of Concern.","authors":"","doi":"10.1177/08977151251364787","DOIUrl":"10.1177/08977151251364787","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"NP8"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799442","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":"Mild Traumatic Brain Injury Alters Hippocampal Sharp-Wave Ripple Properties: Implications in Memory Impairments.","authors":"Brian Noble, Ryota Homma, John I Broussard, Dustin Robinson, Anthony N Moore, Pramod K Dash","doi":"10.1177/08977151261434221","DOIUrl":"10.1177/08977151261434221","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1670-1680"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473964","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":"Preconditioning Effect of Hydrogen Gas on Traumatic Brain Injury.","authors":"Masaya Nakagawa, Satoshi Tomura, Terushige Toyooka, Kazuya Fujii, Arata Tomiyama, Kojiro Wada","doi":"10.1177/08977151261432145","DOIUrl":"10.1177/08977151261432145","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1636-1652"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512829","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":"Subconcussive Preconditioning Modifies Acute Microglial Response and Improves Cognitive Outcomes Post-Concussion.","authors":"Erin D Anderson, Kyulee Kim, Anastasia P Georges, Annika Naveen, Elena Grajales, Daunel V Augustin, David F Meaney","doi":"10.1177/08977151261433816","DOIUrl":"10.1177/08977151261433816","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1653-1669"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512884","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":"Wearable Tracking of Eye and Body Movements During Breaching Training: Toward Real-Time Blast Injury Monitoring.","authors":"Jeremy P Kemmerer, James R Williamson, Joseph Kim, Elizabeth Halford, Hrishikesh M Rao, Christopher J Smalt","doi":"10.1177/08977151261433837","DOIUrl":"10.1177/08977151261433837","url":null,"abstract":"<p><p>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, <i>R</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1623-1635"},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512950","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":"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":"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}