Journal of neurotrauma最新文献

{"title":"Combined Human Neural Stem Cell and Structured Treadmill Walking Therapy Enhances Recovery in a Pediatric Porcine Traumatic Brain Injury Model.","authors":"Sarah L Schantz, Geffrey S Cosgrave, Albino G Schifino, Taylor H LePage, Stephanie T Dubrof, Sydney E Sneed, Savannah R Cheek, Hea Jin Park, Holly A Kinder, Kylee J Duberstein, Jarrod A Call, Erin E Kaiser, Franklin D West","doi":"10.1089/neu.2024.0542","DOIUrl":"10.1089/neu.2024.0542","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, and is indiscriminate in who it affects, including children. Although there are currently no Food and Drug Administration-approved therapeutics, promising results from recent induced pluripotent stem cell-derived neural stem cell (iNSC) studies have demonstrated decreased tissue damage and functional deficits in pre-clinical TBI models. Moreover, while the rest has been traditionally identified as the standard of care following TBI, research now suggests that physical activity postinjury may significantly enhance neuroprotective and regenerative signaling in patients. Combining these two therapies may therefore synergistically improve recovery outcomes in TBI patients. In this study, we evaluated the combined therapeutic efficacy of iNSCs and structured treadmill walking on cellular, tissue, and functional recovery in a translational pediatric pig TBI model. One-month-old piglets received a controlled cortical impact-induced TBI and were randomly assigned to either a PBS (n = 4), PBS + treadmill (n = 4), iNSC (n = 4), or iNSC + treadmill (n = 4) treatment group. Piglets received intraparenchymal transplantations of either iNSCs or PBS 5 days post-TBI. At 1-week post-transplantation, piglets assigned to the treadmill treatment groups began a 12-week progressive walking regimen. Motor function and open field behavior assessments were performed pre-TBI and 12 weeks post-transplantation. Magnetic resonance imaging (MRI) and histological evaluation of collected brain tissue were performed 12 weeks post-transplantation. Immunohistochemistry revealed long-term survival, engraftment, and differentiation of transplanted iNSCs into neurons, astrocytes, and oligodendrocytes in treated piglets. Furthermore, iNSC + treadmill treatment showed increased endogenous neuron and oligodendrocyte survival, increased proliferation of neuroblasts, and decreased populations of reactive astrocytes and immune cells in TBI brain tissue. MRI analysis revealed a significant reduction in lesion volume, midline shift, and white matter degradation with preserved cerebral blood flow following both iNSC and iNSC + treadmill interventions. These cellular and tissue-level effects corresponded with significant motor function recovery as seen through increased step and stride length with decreased stance percentage and time. During open field behavioral assessments, iNSC and iNSC + treadmill-treated piglets demonstrated improved exploratory behaviors. These findings suggest that the combination of iNSCs with structured treadmill walking significantly enhanced TBI recovery beyond the therapeutic potential of iNSCs or exercise alone. Therefore, this novel combination therapy needs to be further explored as a potential transformative treatment option for pediatric TBI patients.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1416-1432"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285021","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":"Post-Concussion Changes in the Functional Brain Connectome Relative to Pre-Injury Baseline: A Prospective Observational Study.","authors":"Nathan W Churchill, Michael G Hutchison, Simon J Graham, Tom A Schweizer","doi":"10.1089/neu.2024.0499","DOIUrl":"10.1089/neu.2024.0499","url":null,"abstract":"<p><p>There is growing concern about the long-term health consequences of concussion, stemming from its high incidence and evidence of post-injury sequelae. This has raised critical questions about clinical assessments of concussion recovery, and whether brain function has fully recovered at medical clearance. The major knowledge gap is only partly addressed by conventional cross-sectional neuroimaging studies, due to a lack of pre-injury baseline imaging. To address this gap, 187 university-level athletes had resting-state functional magnetic resonance imaging collected at pre-season baseline. Of this cohort, 25 were later concussed, with imaging at early symptomatic injury (SYM), medical clearance to return to play (RTP), and 1-3 months post-RTP (POST). An additional 27 uninjured athletes were reimaged as controls. Brain maps were parcellated, and functional connectivity was measured between regions. Mixed models assessed connectivity change at each post-concussion session, along with the moderating effect of time to medical clearance. Concussed athletes had a significantly altered connectome, with predominantly reduced frontotemporal connectivity. Effects were most extensive at SYM, with diminishing but significant effects at RTP and POST, all of which exceeded uninjured control variability (all <i>z</i> ≤ -3.71, <i>p</i> ≤ 0.001). For participants with a longer time to medical clearance, more extensive connectivity decreases were also seen at all post-concussion imaging sessions. These findings provide direct evidence that functional brain recovery lags beyond medical clearance, with more pronounced effects among individuals who have prolonged clinical recovery. Such prospective analyses provide a unique window into biological recovery processes, with major implications for the clinical management of concussion.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1287-1301"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181853","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":"Correlating Magnetoencephalography, Diffusion Kurtosis Imaging, Biomechanics, and Neuropsychology in American Youth Football.","authors":"Natalie M Bell, Fang F Yu, Yin Xi, Amy L Proskovec, James M Holcomb, Sahil Chilukuri, Jillian E Urban, Christopher Vaughan, Jesse C DeSimone, Ben Wagner, Mark A Espeland, Alexander K Powers, Christopher T Whitlow, Joel D Stitzel, Joseph A Maldjian, Elizabeth M Davenport","doi":"10.1089/neu.2024.0222","DOIUrl":"10.1089/neu.2024.0222","url":null,"abstract":"<p><p>This study investigated the association between repetitive head impacts (RHIs) and multimodal neuroimaging, biomechanical, and neuropsychological data in 72 youth football players and 17 controls, aged 8-12 years. Helmet sensors measured RHI exposure while imaging and psychological data were collected before and after the season. Risk-weighted exposure metrics were calculated to quantify cumulative RHI exposure. Changes in magnetoencephalography (MEG) and diffusion kurtosis imaging were analyzed by calculating voxel-wise difference, and z-score maps were thresholded with respect to controls. Using linear regression, statistically significant positive associations were observed between abnormally increased MEG-measured theta (5-7 Hz) power and RHI measures. No associations were found between RHI and other neuroimaging metrics. Football players and controls exhibited significant yet divergent associations between alpha (8-12 Hz) power as well as mean kurtosis and neuropsychological changes. These findings indicate a potential association between youth football players' exposure to RHI and neurophysiological alterations.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1302-1318"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997556","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":"Trajectory of Post-Traumatic Stress During the First Year after Pediatric Traumatic Brain or Orthopedic Injury.","authors":"Linda Ewing-Cobbs, Charles S Cox, Amy Clark, Heather T Keenan","doi":"10.1089/neu.2024.0578","DOIUrl":"10.1089/neu.2024.0578","url":null,"abstract":"<p><p>Up to 50% of children sustaining physical injury develop post-traumatic stress symptoms (PTSS). Most studies of PTSS have not included patients with traumatic brain injury (TBI); consequently, the influence of injury type and severity on the longitudinal course of PTSS is unclear. To address this gap, we completed a longitudinal prospective cohort study examining the trajectory of self-reported PTSS severity during the first year after TBI or orthopedic injury (OI). Within a biopsychosocial framework, we examined PTSS in relation to injury variables, demographic characteristics, and pre-injury child and family functioning. Patients ages 9-15 years with TBI or OI were recruited from two level I pediatric trauma centers. Online surveys were completed as soon as possible following injury (mdn = 8 days). Caregivers rated pre-injury family, sociodemographic, and child characteristics. Follow-up surveys assessing children's self-reported PTSS using the Children's PTSD Symptom Scale (CPSS) were scheduled 3,6, and 12 months after injury. English-speaking families completed surveys either online or by telephone interview; Spanish-speaking families were interviewed. Baseline surveys were completed by 303 families; 265 (87%) completed at least 1 follow-up and comprised the cohort. General linear mixed models examined the influence of injury group and severity, age, sex, and time of assessment on CPSS scores. Pre-injury estimates of child and family functioning were examined as predictors in supplemental models. Participants (72% boys, mean [SD] age 12.7 [1.9] years) included 204 with TBI (76 mild, 82 complicated-mild/moderate, 46 severe) and 61 with OI. Relative to OI, patients with TBI had significantly elevated mean CPSS scores at 3 (3.7 points, 95% confidence intervals [CI]: 1.1, 6.3); 6 (3.2, 95% CI: 0.7, 5.7) and 12 months (2.3, 95% CI: 0.1, 4.5). The primary model indicated that TBI severity had a nonlinear relation with CPSS. Mild TBI (mTBI) had the highest mean scores; with significant differences relative to OI at 3 (4.6 points, 95% CI: 1.6, 7.6); 6 (5.7, 95% CI: 2.7, 8.6) and 12 months (3.2, 95% CI: 0.6, 5.8). This model also revealed that adolescent females had higher CPSS scores than children or adolescent males. Differences relative to younger males at 6 and 12 months were 4.9 (95% CI: 1.6, 8.3) and 5.0 points (95% CI: 2.1, 8.0). In supplemental models, higher symptom burden was associated with poorer baseline family functioning and with higher levels of children's pre-injury anxiety, affective problems, and conduct problems. PTSS persisted for a significant minority of patients with TBI across the first year of recovery, particularly those with mTBI. Screening should emphasize risk factors to target patients with the greatest need for trauma-focused intervention. Cost-effective, scalable, evidence-based trauma-focused interventions are essential to meet American College of Surgeons standards to provide psychological screening and treatme","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1382-1393"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997975","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":"Sexually Dimorphic Responses Reveal Multifaceted Benefits of Glibenclamide in Traumatic Brain Injury.","authors":"Anupama Rani, Sudhanshu P Raikwar, Wonsuk Yoo, Saif Ahmad, Vincent A Vagni, Keri L Janesko-Feldman, Shaun W Carlson, Adam Eberle, Margaux Miller, John Helm, Joshua Catapano, Benjamin E Zusman, Shashvat Desai, Raemier Anne M Javelosa, Semeon Afework, Erin Audrey McNally, Gary Kohanbash, Dhivyaa Rajasundaram, Michael F Waters, Andrew Ducruet, Ashutosh Jadhav, Aditya Kumar, Chia-Ling Phuah, Patrick M Kochanek, Ruchira M Jha","doi":"10.1089/neu.2024.0232","DOIUrl":"10.1089/neu.2024.0232","url":null,"abstract":"<p><p>Sex disparities in traumatic brain injury (TBI) remain poorly understood. Previous data suggest that males are more susceptible to acute secondary injury processes and cell death, whereas females are more vulnerable chronically. Additional sex-based differences have been reported depending on injury model/severity and post-traumatic neurodegeneration. This gap in understanding limits therapy translation. We previously demonstrated sex-based differences in genetic modulation of a key pathway of secondary injury in TBI, sulfonylurea-receptor 1 (SUR1). Glibenclamide (GLI, SUR1-inhibitor) has shown promise in pre-clinical and early clinical studies of TBI and stroke. Here, we evaluated GLI's modulation of multifaceted TBI outcomes across sex for the first time. In total, 120 mice were randomized to controlled cortical impact (CCI) ± GLI or vehicle (dimethyl sulfoxide, DMSO). Either vehicle or GLI treatment was administered post-CCI using an intraperitoneal (IP) loading dose (10 µg/mouse, 10 min post-TBI), followed by a 7-day subcutaneous maintenance infusion at 0.5 µL/h using ALZET mini-osmotic pumps (1007D, Durect Corp.). Mice were tested for cognitive function (Morris water maze, MWM), motor function (rotarod), anxiety (elevated plus maze, EPM), immunofluorescence markers of neurodegeneration (TAU, TDP43), neurogenesis (SOX2, Ki67), angiogenesis (VEGFA), and cerebral blood flow (CBF) to interrogate behavioral, molecular, and physiological effects of TBI and therapy. Different measures within behavioral, immunofluorescence, and CBF outcomes varied across sex, either post-CCI and/or in response to GLI. Motor impairment had baseline differences across sex post-CCI. In both sexes, behavioral deficits were improved by GLI. The effect of GLI on behavior was moderated by sex, with greater benefit in males versus females, including improved MWM latency (<i>p</i>_{treatment*sex_interaction} < 0.0001) and rotarod latency (<i>p</i>_{treatment*sex_interaction} = 0.016, revolutions per minute, <i>p</i>_{treatment*sex_interaction} = 0.03). Males had increased anxiety post-CCI (EPM); GLI was beneficial across sexes. TDP43 and TAU in several brain regions were increased 72 h post-CCI (males>females, all <i>p</i> < 0.0001). These remained markedly elevated only in females by 21 days, whereas TAU in males decreased without treatment. GLI downregulated TDP43 and TAU across sex and brain region (all <i>p</i> < 0.01-0.0001). In females only, DMSO had similar effects as GLI on TDP43 and TAU. SOX2 was increased in the dentate gyrus (DG) only in males post-CCI (<i>p</i>_72h < 0.01, <i>p</i>_21d < 0.001). GLI increased DG SOX2 in females (<i>p</i>_72h < 0.05, <i>p</i>_21d < 0.001). GLI increased VEGFA at 72 h across sexes. CCI reduced CBF acutely in both sexes; in males, GLI improved this by 21 days (<i>p</i> = 0.031). In females, both GLI and DMSO-vehicle benefited CBF versus untreated-CCI. We demonstra","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1319-1344"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285023","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":"Frequency of Diffuse Axonal Injury and Its Outcomes in Severe Traumatic Brain Injury (sTBI): A Systematic Review and Meta-Analysis.","authors":"Vivek Sanker, Emil O R Nordin, Philip Heesen, Poorvikha Satish, Afia Salman, Venkata Vamshi Krishna Dondapati, Simon Levinson, Atman Desai, Harminder Singh","doi":"10.1089/neu.2024.0469","DOIUrl":"10.1089/neu.2024.0469","url":null,"abstract":"<p><p>While it is established that diffuse axonal injury (DAI) is a leading cause of death or disability among patients with traumatic brain injury (TBI), less is known about the frequency of DAI in patients with severe TBI (sTBI). Additionally, little is known about the mortality rate and proportion of males/females among patients with both sTBI and DAI. We conducted a systematic literature search in the databases EMBASE Ovid, PubMed, Scopus, and Web of Science Advance from inception until April 22, 2024. No filters or language restrictions were applied. Two reviewers (A.S. and P.S.) independently screened the obtained abstracts and full texts. We included full-text studies that reported the frequency of DAI after TBI or any measure of association between DAI and clinical outcome (e.g., death, Glasgow Outcome Scale). Animal studies, reviews, and non-original research articles were excluded. We qualitatively described the results of the included studies. Thirty-seven studies met our inclusion criteria: 18 retrospective, 18 prospective, and 1 was both retrospective and prospective, representing studies from 14 countries. Thirty-three were single-center studies, and four were multicenter. Five studies were exclusively conducted among pediatric patients, while the remaining 32 included adults. The pooled proportion of DAI among sTBI patients was 0.60 (95% confidence interval [CI]: 0.39, 0.78]), <i>I</i>² = 98%. The pooled mortality among patients with both sTBI and DAI is 0.16 [95% CI: 0.07, 0.30], <i>I</i>² = 12%. The pooled proportion of males among individuals with both sTBI and DAI was 0.81 [95% CI: 0.76, 0.85], <i>I</i>² = 46%. DAI is common in patients with sTBI. The comorbid state of having both sTBI and DAI can be life-threatening and is more often seen in males than females, possibly due to the increased tendency of males to partake in risky behaviors that increase the likelihood of head trauma. There might be a difference in outcome after DAI between the pediatric and adult patient populations, possibly due to increased plasticity of brain tissue in younger patients.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1243-1255"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248344","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":"Self-Reported Cognitive Difficulties and Their Modifiable Risk Factors in Former Elite Male Rugby League Players.","authors":"Katherine Grellman, Oliver J Smith, Douglas P Terry, Kenneth L Quarrie, Grant L Iverson, Andrew J Gardner","doi":"10.1089/neu.2024.0543","DOIUrl":"10.1089/neu.2024.0543","url":null,"abstract":"<p><p>Participation in collision and contact sport in Australia-specifically rugby league-is popular. With recent attention to the possible long-term health consequences of head impact exposure during a contact or collision sport career, the importance of understanding the contribution of modifiable risk factors as they relate to cognitive function has been highlighted. Risk factors for cognitive decline in the general population include cardiovascular health, sleep disorders, chronic pain, depression, anxiety, smoking, physical impairment, and physical inactivity. This study examined the associations between these risk factors and self-reported cognitive function in 130 former elite male rugby league players in Australia. Respondents were recruited through a survey distributed through former player groups and via word of mouth. Self-reported cognitive function was assessed using the Quality of Life in Neurological Disorders-Applied Cognition General Concerns questionnaire. Risk factors for cognitive decline were self-reported, with questions collated from multiple validated sources, with each selected to explore specific categories of cognitive function. They included: questions from the Football Players Health Study at Harvard; The Australian Mental Health and Wellbeing Survey 2007; the Patient Reported Outcome Measurement Information System Item Banks for Pain Interference and Physical Function; and the Patient Health Questionnaire. Of the 130 participants, 43.1% (<i>n</i> = 56) reported perceived cognitive impairment. When adjusted for age and number of concussion-related signs and symptoms experienced during their career, predictors of perceived cognitive difficulties included less than 5 h of sleep on average, history of stroke, current clinical symptoms of anxiety, physical impairment, and number of risk factors. The number of concussion-related signs and symptoms experienced was not related to perceived cognitive impairment, although it was associated with specific risk factors. Early education and intervention by medical professionals to manage these risk factors may provide a pathway for improving perceived cognitive health and functioning in former elite male rugby league players in the future.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1453-1463"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029462","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":"Prognostic Value of Blood-Based Protein Biomarkers in Traumatic Brain Injury: A Living Systematic Review and Meta-Analysis.","authors":"Stefania Mondello, Krisztina Amrein, Endre Czeiter, Giuseppe Citerio, Ramon Diaz-Arrastia, Guoyi Gao, Alfonso Lagares, Geoffrey T Manley, David K Menon, Virginia Newcombe, Jussi P Posti, Lindsay Wilson, Henrik Zetterberg, Ewout W Steyerberg, Andras Buki, Andrew I R Maas","doi":"10.1089/neu.2024.0620","DOIUrl":"10.1089/neu.2024.0620","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Circulating biomarkers might improve the prediction of outcomes in patients with traumatic brain injury (TBI) beyond current approaches. Robust and up-to-date evidence is required to support their clinical utility and integration into medical practice to guide decision-making. Our objective was to critically appraise the existing evidence for six core blood-based TBI biomarkers (S100 calcium-binding protein B, glial fibrillary acidic protein [GFAP], neuron-specific enolase, ubiquitin C-terminal hydrolase-L1 [UCH-L1], tau and neurofilament proteins), in predicting outcome after TBI. Electronic databases, including Medline and Embase, were searched for articles published from their inception to October 2023. Studies were included if they evaluated the accuracy of blood biomarker concentrations at hospital presentation for outcome prediction in adult patients with TBI. Outcomes assessed were mortality, Glasgow Outcome Scale (GOS)/GOS extended (GOS-E), or the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Study selection, data extraction, and quality assessment using the modified Quality Assessment of Prognostic Accuracy Studies tool were performed by two authors independently, with disagreements being resolved through discussion or arbitration. If appropriate, a meta-analysis was conducted by calculating the weighted summary area under the curve (AUC) and using a bivariate regression model. Of 12,792 retrieved records, 32 articles, including 7481 patients with TBI, were selected as relevant. Two biomarkers showed strong associations with in-hospital and 6-month mortality: GFAP (unadjusted pooled AUC 0.81 [95% confidence interval [CI] 0.75-0.87] and 0.82 [0.80-0.85], respectively) and UCH-L1 (0.80 [0.74-0.85] and 0.83 [0.77-0.88]). Their addition to models that included established risk factors consistently improved the predictive value, though models and performance varied substantially across studies. In four studies measuring both markers, UCH-L1 outperformed GFAP in improving risk stratification when added to established prediction models. At ∼1.5 ng/mL (five studies), the summary sensitivity of GFAP for predicting mortality was 78% (95% CI 67-85%), and the summary specificity was 79% (95% CI 64-89%). The other assessed biomarkers had fair to good performance in mortality prediction with unclear added benefits. Neurofilament light (NfL) (three studies) demonstrated the strongest association in predicting a 6-month poor outcome (GOS-E ≤4; GOS ≤3) (unadjusted pooled AUC 0.81 [95% CI 0.75-0.87]), whereas the other assessed biomarkers had a fair performance with unclear or irrelevant added value. All core biomarkers had only marginal or no association with incomplete recovery and post-concussion symptoms/syndrome, as assessed by RPQ. Serious problems were found in the design and analysis of many of the studies. We conclude that admission measurements of core blood TBI biomarkers, in particular GFAP and UCH-L1, are strongly associated w","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1256-1286"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159619","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":"CMX-2043 Treatment Limits Neural Injury Pathophysiology and Promotes Neurological and Cognitive Recovery in a Pediatric Porcine Traumatic Brain Injury Model.","authors":"Sarah L Schantz, Taylor H LePage, Stephanie T Dubrof, Sydney E Sneed, Savannah R Cheek, Hea Jin Park, Deborah A Barany, Holly A Kinder, Kylee J Duberstein, David A DeWahl, Alexander B Baguisi, Jerry O Stern, Erin E Kaiser, Franklin D West","doi":"10.1177/08977151251363584","DOIUrl":"https://doi.org/10.1177/08977151251363584","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) represents a major global health issue contributing to significant disability and mortality. The TBI-induced secondary injury cascade, characterized by neuroinflammation, neural cell death, and tissue damage, results in lifelong functional deficits. Alpha-<i>N</i>-[(R)-1, 2-dithiolane-3-pentanoyl]l-glutamyl-l-alanine (CMX-2043) is a novel alpha lipoic acid (ALA)-based therapeutic that has neuroprotective, anti-apoptotic, and anti-inflammatory properties that mitigate cellular, tissue, and functional deficits following TBI. In this study, we evaluated the therapeutic efficacy of CMX-2043 on neural injury severity and functional recovery in a clinically relevant porcine TBI model. CMX-2043 was administered 1-h post-TBI subcutaneously (SQ; <i>n</i> = 8) or intravenously (IV; <i>n</i> = 8) for a total of 5 days. Control piglets (placebo; <i>n</i> = 11) received saline subcutaneously. Magnetic resonance imaging (MRI), immunohistochemistry analysis, modified Rankin Scale (mRS) neurological evaluation, and social recognition testing (SRT) were evaluated up to 42 days post-TBI. MRI revealed that SQ and IV CMX-2043 administration reduced hemispheric swelling and atrophy, lesion volume, midline shift, and intracerebral hemorrhage and preserved diffusivity, cerebral blood flow, and white matter integrity. CMX-2043-mediated neuroprotection and regeneration were indicated by increased neural cell density, decreased neuroinflammation, and enhanced neurogenesis following SQ and IV administration. These cellular and tissue-level changes corresponded with reduced neurological deficits and rapid cognitive recovery as indicated by improved mRS and SRT results, respectively. Collectively, these results observed in a translational large animal porcine model suggest that CMX-2043 holds significant clinical value to potentially mitigate TBI pathophysiology and promote functional recovery.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742284","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> Clinical Assessment of Days 1-14 for the Characterization of Traumatic Brain Injury: Recommendations from the 2024 NINDS Traumatic Brain Injury Classification and Nomenclature Initiative Clinical/Symptoms Working Group.","authors":"Narinder Kapur","doi":"10.1177/08977151251363496","DOIUrl":"https://doi.org/10.1177/08977151251363496","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731800","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}