Journal of neurotrauma最新文献

{"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}

{"title":"Machine Learning in Traumatic Brain Injury: Dynamic Prediction from Continuous Physiological Monitoring and ICU Data.","authors":"Marcus Roland Victor Gustafsson, Tomasz Benedykt Kuliński, David Bark, Andre Wyzykowski, Elham Rostami","doi":"10.1177/08977151261486820","DOIUrl":"https://doi.org/10.1177/08977151261486820","url":null,"abstract":"<p><strong>Background: </strong>Continuous physiological monitoring in neurocritical care generates large volumes of high-frequency time-series data that remain underutilized in routine traumatic brain injury (TBI) management. Machine learning (ML) approaches applied to these data have emerged as a promising strategy for dynamic prediction of secondary brain injury and individualized clinical decision support.</p><p><strong>Methods: </strong>This narrative review summarizes current ML applications based on continuous physiological monitoring in TBI and related neurocritical care populations. A structured PubMed search supplemented by manual reference screening identified studies published through January 2026. Included studies applied ML methods to continuously acquired physiological signals such as intracranial pressure (ICP), arterial blood pressure (ABP), cerebral perfusion pressure (CPP), and related intensive care unit data.</p><p><strong>Results: </strong>Thirty-four studies were identified, of which 26 met core inclusion criteria focused on continuous physiological monitoring. The most common applications were prediction of intracranial hypertension events, mortality, and functional outcome. Fewer studies addressed arterial hypotension prediction or unsupervised clustering approaches. Recent work demonstrates a transition from static admission-based prognostic models toward dynamic prediction using continuously updated physiological data. Deep learning architectures, including recurrent neural networks and transformers, were increasingly used for high-resolution time-series analysis. However, substantial heterogeneity exists in study design, preprocessing methods, prediction targets, and validation strategies. Most studies relied on retrospective observational data and internal validation, while prospective evaluation and workflow-integrated implementation remain limited.</p><p><strong>Conclusion: </strong>ML approaches using continuous physiological monitoring show significant potential for dynamic prediction and decision support in TBI care. Future progress will depend on multicenter external validation, standardized methodological frameworks, prospective evaluation, and integration into real-time neurocritical care workflows.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261486820"},"PeriodicalIF":3.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919981","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":"Considerations for Mesenchymal Stem Cell-Derived Small Extracellular Vesicle-Based Clinical Treatment of Spinal Cord Injury.","authors":"Karen L Lankford, Masahito Nakazaki, Ryosuke Hirota, Jeffery D Kocsis","doi":"10.1177/08977151261483981","DOIUrl":"https://doi.org/10.1177/08977151261483981","url":null,"abstract":"<p><p>A large body of animal studies across multiple laboratories has found that a subset of small extracellular vesicles (sEVs) derived from mesenchymal stromal cells (MSC-sEVs) referred to as exosomes can improve functional recovery after spinal cord injury (SCI). Sufficient pre-clinical data have been accumulated to consider how MSC-sEVs might be used clinically for the treatment of SCI. This review discusses: (1) the SCI patient population which may benefit from MSC-sEVs treatments, (2) potential sources of MSCs for production of clinically useful MSC-sEVs, (3) dosaging of MSC-sEVs required for therapeutic efficacy, (4) timing and method of delivery of the sEVs, (5) cell targets of MSC-sEVs and their mechanism of action, (6) possible protocols for producing clinically useful quantities of MSC-sEVs, and (7) the criteria for evaluating an MSC-sEVs treatment product. We conclude with some thoughts about potential protocols for clinical trials of MSC-sEVs treatment for SCI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261483981"},"PeriodicalIF":3.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919984","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":"Younger Age of First Exposure to American Football Is Associated with Worse Informant-Reported Clinical Outcomes in Older Age Brain Donors.","authors":"Sophia B Nosek, Stephanie Gonzalez Gil, Bobak Abdolmohammadi, Rachael Layden, Christopher J Nowinski, Yorghos Tripodis, Brett M Martin, Joseph N Palmisano, Alcy Torres, Brigid C Dwyer, Doug I Katz, Lee E Goldstein, Robert C Cantu, Robert A Stern, Thor D Stein, Ann C McKee, Jesse Mez, Michael L Alosco, Daniel H Daneshvar","doi":"10.1177/08977151261424707","DOIUrl":"10.1177/08977151261424707","url":null,"abstract":"<p><p>Although the younger age of first exposure (AFE) to American football has not been associated with neurodegenerative pathology, AFE has been associated with clinical symptoms. However, the literature is mixed. We examined the association between AFE to football and clinical outcomes before and after age 60 at death, to isolate the potential role of decreased neuropathological resilience in older age. This study included 677 deceased male football players who donated their brains to the Understanding Neurologic Injury and Traumatic Encephalopathy Brain Bank. Informants completed modified scales assessing cognition, function, behavior, and neuropsychiatric features with dementia adjudicated through consensus conferences. Regressions tested the association between AFE and dementia, chronic traumatic encephalopathy (CTE) pathology, and each scale, adjusted for multiple testing. Analyses were stratified by age 60, adjusting for age at death, duration of play, and neuropathology. Most donors (mean age = 60.9, standard deviation = 19.8) played college or professional football (<i>n</i> = 509, 76%). CTE was the most prevalent neuropathology (<i>n</i> = 471, 70%). AFE was not associated with neurodegenerative disease pathology. Among those older than 60 at death, younger AFE was associated with cognitive composite score impairment (odds ratio: 0.897, 95% confidence interval [CI]: 0.814-0.988, <i>p</i> = 0.027) and worse cognitive (beta: 0.04, 95% CI: 0.01-0.069, <i>p</i> = 0.009), neurobehavioral (beta: 0.032, 95% CI: 0.002-0.062, <i>p</i> = 0.035), and neuropsychiatric (beta: 0.032, 95% CI: 0.00-0.064, <i>p</i> = 0.048) composite scores. Younger AFE was only associated with worse informant-reported clinical outcomes in older deceased football players, independent of neurodegeneration. Our findings offer a potential explanation for the mixed literature on AFE and clinical outcomes. The effects of AFE may only manifest in older adults when cognitive reserve is depleted, neuropathological resilience is reduced, or age-related vulnerabilities interact with prior head injury exposure, worsening clinical outcomes.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1456-1470"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194789","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":"Association Between Individualized Intracranial Pressure Thresholds and Long-Term Outcomes in Moderate-to-Severe TBI: A CAHR-TBI Multicenter Study.","authors":"Kevin Y Stein, Donald Griesdale, Mypinder Sekhon, Francis Bernard, Clare Gallagher, Eric P Thelin, Rahul Raj, Marcel Aries, Logan Froese, Francois Mathieu, Andreas Kramer, Frederick A Zeiler","doi":"10.1177/08977151261481325","DOIUrl":"https://doi.org/10.1177/08977151261481325","url":null,"abstract":"<p><p>Current neurocritical care relies on fixed, population-based intracranial pressure (ICP) thresholds, which fail to account for inter-individual variability or the dynamic nature of cerebral physiology. Individualized ICP (iICP) thresholds have emerged as a potential personalized alternative but have largely relied on complete recording periods, limiting their derivation to post-hoc calculations and preventing continuous real-time estimation. Recently, a novel algorithm capable of continuously deriving iICP was developed; however, this algorithm has not yet been validated beyond a single-center cohort, and its prognostic utility remains uncertain. Therefore, the goals of this study were to externally validate the performance of this continuous iICP algorithm and to evaluate the prognostic utility of continuously derived iICP compared with current guideline-based ICP thresholds. A retrospective multicenter study was conducted using high-resolution physiologic datasets from the CAHR-TBI collaborative. iICP was derived using the recently developed continuous iICP algorithm. Algorithm performance was externally validated by assessing derivation yields and associated quality metrics and comparing with those reported in the original study that introduced the algorithm. Outcome associations were evaluated using mean hourly dose of ICP above iICP and guideline-based thresholds. Logistic regression models were used to assess and compare prognostic performance, with discrimination quantified using optimism-corrected area under the receiver operating characteristic curve and added predictive value assessed using Nagelkerke's R2. Finally, intensity-duration heatmaps were generated to characterize the relationship between iICP-based insult burden and clinical outcomes. The continuous iICP algorithm demonstrated consistent performance across parameter settings compared with the original study, supporting its external validity. Select hybrid iICP configurations, defaulting to 20 mmHg or 22 mmHg during periods where iICP could not be identified, outperformed guideline-based ICP thresholds in prognostic models. Heatmap analyses demonstrated a graded relationship between iICP-defined insult burden and outcome, with greater burden of ICP above iICP associated with poorer outcomes. Overall, iICP represents a promising adjunct to conventional guideline-based ICP management in neurocritical care. The findings of this study suggest potential clinical benefit from iICP-supplemented ICP management; however, prospective randomized controlled trials will be required to determine whether such an approach translates into meaningful improvements in patient outcomes.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"8977151261481325"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874477","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":"Behavioral Deficits and Cortical Network Dysfunction Following Repeated Mild Traumatic Brain Injuries.","authors":"Natalie J Pinkowski, Brandi R Hess, Johann M Pacheco, Devon S Hatcher, Myah McDonald, Adrienne N Swindle, Raycarlo Laboy Ramirez, Matthew Situ, Taha Abdeljawad, Carissa J Mehos, Andrew R Mayer, Sam McKenzie, Russell A Morton","doi":"10.1177/08977151261425217","DOIUrl":"10.1177/08977151261425217","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) is a prevalent health concern, with more than 2.5 million cases occurring annually in the United States. Acute signs and symptoms of mTBIs may involve physical symptoms, as well as emotional, cognitive, and sleep-related issues. The underlying mechanisms of these symptoms remain elusive. Here, we describe that repeated closed skull mTBIs in mice are associated with acute behavioral deficits. We found that optogenetic-induced spreading depolarizations (SDs) are associated with similar behavioral deficits. Using <i>in vivo</i> electrophysiology, we confirmed the depression of cortical network activity following optogenetic-induced SDs. The timing of the high-frequency activity recovery coincided with the recovery of voluntary movement. Following the depression, there was a prolonged period of increased power in low frequencies (<30 Hz). Cortical dysfunction coincided temporally with motor behavioral deficits in the neurological severity score tasks. Our study provides evidence that repeated mTBIs or SDs are associated with worse behavioral deficits.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1506-1519"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457920","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}