Journal of neurotrauma最新文献

{"title":"Starting with the End in Mind: Recommendations to Optimize Implementation of a Novel TBI Classification from the 2024 NINDS TBI Classification and Nomenclature Workshop's Knowledge to Practice Working Group.","authors":"Peter Bragge, Molly McNett, Mark Bayley, Maureen Dobbins, Risa Nakase-Richardson, Corinne Peek-Asa, Alexis F Turgeon, Hibah Awwad, Kristen Dams-O'Connor, Adele Doperalski, Andrew Maas, Mike McCrea, Nsini Umoh, Geoff Manley","doi":"10.1089/neu.2024.0576","DOIUrl":"10.1089/neu.2024.0576","url":null,"abstract":"<p><p>The Knowledge to Practice Working Group (K2P WG) was one of six expert groups convened in early 2023 to plan the 2024 National Institute of Neurological Disorders and Stroke Traumatic brain injury (TBI) Classification and Nomenclature Workshop. Recognizing that implementation of revised classification systems is essential to achieve intended impact, the K2P WG's key aims were to foster shared understanding of knowledge translation (KT), build capacity for implementation of a revised TBI classification system, identify and prioritize KT actions, implementation steps and audiences; and make recommendations to advance implementation. The cornerstone of this work was a focused survey to identify \"who needs to do what differently,\" while prioritizing potential implementation actions. Survey findings, dialogue with other working groups, stakeholder discussions, and public feedback were also utilized to support implementation of the revised Clinical, Biomarker, Imaging-Modifiers and retrospective TBI classification system. Forty researchers across five working groups responded to the survey (Response Rate = 59.7%). Fifty-two unique implementation actions were identified. The top 15 priorities across the five working groups comprised six pertaining to clinical practice (e.g., change Glasgow Coma Scale [GCS] assessment); seven focusing on research (e.g., develop tools for measuring psychological and environmental factors); and one each on lived experience (simplified language for patients and families) and other settings (insurance company support for biomarker testing). Twenty-seven stakeholder groups and 18 target settings were identified as being most impacted by the revised classification system. Key recommendations included: develop guidelines based on systematic reviews, clearly explain the rationale for the change, develop implementation toolkits with input from all stakeholders, and embed the new classification in a learning health system database to facilitate implementation strategies based on audits, feedback, and cost-effectiveness analyses.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1096-1108"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970136","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":"Blood-Based Biomarkers for Improved Characterization of Traumatic Brain Injury: Recommendations from the 2024 National Institute for Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Blood-Based Biomarkers Working Group.","authors":"Jeffrey J Bazarian, Henrik Zetterberg, András Buki, Bradley A Dengler, Ramon Diaz-Arrastia, Frederick K Korley, Rachel Lazarus, Timothy B Meier, Stefania Mondello, Kasey Moritz, David O Okonkwo, Linda Papa, James B Phillips, Jussi P Posti, Ava M Puccio, Stephanie Sloley, Ewout Steyerberg, Kevin K Wang, Hibah O Awwad, Kristen Dams-O'Connor, Adele Doperalski, Andrew I R Maas, Michael A McCrea, Nsini Umoh, Geoffrey T Manley","doi":"10.1089/neu.2024.0581","DOIUrl":"10.1089/neu.2024.0581","url":null,"abstract":"<p><p>A 2022 report by the National Academies of Sciences, Engineering, and Medicine called for a Traumatic Brain Injury (TBI) Classification Workshop by the National Institutes of Health (NIH) to develop a more precise, evidence-based classification system. The workshop aimed to revise the Glasgow Coma Scale-based system by incorporating neuroimaging and validated blood biomarker tests. In December 2022, the National Institute for Neurological Disorders and Stroke formed six working groups of TBI experts to make recommendations for this revision. This report presents the findings and recommendations from the blood-based biomarker (BBM) working group, including feedback from the workshop and subsequent public review. The application of BBMs in a TBI classification system has potential to allow for a more adaptable and nuanced approach to triage, diagnosis, prognosis, and treatment. Current evidence supports the use of glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1, and S100B calcium-binding protein (S100B) to assist in reclassification of TBI at acute time points (0-24 h) primarily in emergency department settings, while neurofilament light chain (NfL), GFAP, and S100B have utility at subacute time points (1-30 days) in-hospital and intensive care unit settings. Blood levels of these biomarkers reflect the extent of structural brain injury in TBI and may be useful for describing the extent of structural brain injury in a classification system. While there is insufficient evidence to support a role for BBMs at chronic time points (>30 days), emerging evidence suggests that NfL and phosphorylated tau may have a potential future role in this regard. For inclusion in a revised TBI classification system, BBM assays must have appropriate age- and sex-specific reference ranges, be harmonized across platforms, and achieve high analytical precision, including accuracy, linearity, detection limits, selectivity, recovery, reproducibility, and stability. Improving transparency in BBM assay development can be achieved through large-scale data sharing of methods and results. Future research should focus on methods for promoting clinical adoption of BBM results, correlating BBMs with advanced neuroimaging, and on discovering new biomarkers for improved diagnosis and prognosis.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1065-1085"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111019","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":"Predictive Factors Affecting the Need for Mechanical Ventilation in Acute Traumatic Cervical Spinal Cord Injury.","authors":"Chonnawee Chaisawasthomrong, Atthaporn Boongird","doi":"10.1089/neu.2025.0006","DOIUrl":"10.1089/neu.2025.0006","url":null,"abstract":"<p><p>Acute traumatic cervical spinal cord injuries (TCSCI) are associated with significant mortality and morbidity, particularly when complicated by neurogenic respiratory failure. While upper cervical-level injuries are established risk factors for mechanical ventilation, patients with acute injuries below the fifth cervical level without significant chest trauma may also require ventilatory support. However, reliable early predictors remain unclear. This study aims to identify the primary predictors of early mechanical ventilation needs in patients with acute TCSCI. We conducted a retrospective analysis of 148 cases of TCSCI treated between 2019 and 2022. Among these, 27 cases (18.24%) required ventilatory support. Multivariate analysis revealed that a compression grade of 2 or higher, exceeding 25% on Computed Tomography (CT) (adjusted odds ratio [aOR]: 10.18; 95% CI: 2.03-50.94; <i>p</i> < 0.001), and a cord contusion length spanning at least two levels on Magnetic Resonance Imaging (MRI) (aOR: 2.11; 95% CI: 1.06-4.22; <i>p</i> = 0.03) were significant independent predictors. CT-based spinal cord compression measurements showed a strong correlation with MRI findings (linear regression coefficient = 0.88, 95% CI: 0.80-0.96; Spearman's rho = 0.90; both <i>p</i> < 0.001). The regression line was closely aligned with the equality line, indicating CT can reliably approximate MRI. Noninferiority testing revealed no significant difference in predicting mechanical ventilation risk between modalities (<i>p</i> = 0.21). Survival analyses stratified by compression grades demonstrated similar predictive performance, with higher compression grades (2-4) associated with increased risk of ventilation over time. These findings suggest that the degree of cord compression and cord contusion length are reliable, noninvasive predictors of the need for mechanical ventilation in TCSCI, emphasizing the importance of early recognition, cost-effective health care management, and prognostic counseling. The Subaxial Injury Classification and Severity Scale demonstrated borderline significance (sensitivity 81.5%, specificity 87.6%). The study found that patients with >25% cervical spinal cord compression had significantly poorer outcomes compared to those with ≤25% compression, including longer hospital stays, lower survival rates, worse pre-treatment neurological status, and higher complication rates. Surgical treatment, particularly the posterior approach, was more common in the >25% compression group; however, post-treatment neurological improvement was observed only in cases of grade 2 degree compression, not grades 3 and 4 in CT and MRI. In contrast, the ≤25% compression group demonstrated better outcomes, with greater post-treatment improvement. [Figure: see text].</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484690","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":"Inflammatory, White Matter, and Neurodegenerative Mechanisms in Fluid Ability Decrements in Chronic Mild-to-Moderate Traumatic Brain Injury.","authors":"Samantha H Penhale, Abigail B Waters, Shoumi Sarkar, Leah E McQuillan, John Maczuzak, Somnath Datta, Damon Lamb, Claudia Robertson, Richard Rubenstein, Amy K Wagner, Firas Kobeissy, Kevin K W Wang, John B Williamson","doi":"10.1089/neu.2024.0566","DOIUrl":"https://doi.org/10.1089/neu.2024.0566","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) affects millions globally each year, with mild TBI comprising about 75% of cases. While most mild TBI symptoms are resolved within 3 months, some patients experience persistent issues. This study aimed to identify underlying mechanisms contributing to decrements in fluid cognitive abilities in chronic (>6 months) mild-to-moderate TBI. Specifically, the study focused on the relationships between cognitive performance, white matter integrity, TBI-related symptoms, and blood biomarkers, which are thought to be indicative of biological processes including neuronal injury (neurofilament light [NF-L], neurofilament heavy, ubiquitin C-terminal hydrolase-L1), vascular injury (vascular endothelial growth factor A), glial injury (glial fibrillary acidic protein [GFAP]), neurodegeneration (tau, phosphorylated-tau), immune response (GFAP immunoglobulin G), and inflammation (tumor necrosis factor-α, interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, interferon-γ, and macrophage inflammatory protein-1α). The final study sample included 57 participants (42 males, 15 females) aged 19-59 with a history of chronic, remote mild-to-moderate TBI. Participants underwent cognitive and behavioral testing, neuroimaging, and a blood draw. Diffusion-weighted magnetic resonance imaging was used to assess white matter integrity in tracts connecting frontal and parietal regions with fractional anisotropy utilized as the metric. Blood samples were analyzed for TBI-related biomarkers. The study found that higher fluid cognition scores were associated with higher white matter integrity in frontal-parietal networks, fewer reported TBI-related symptoms, and mixed biomarker and cytokine levels. Inflammatory processes were linked to lower fractional anisotropy in white matter pathways, more reported symptoms, and increased biomarkers of injury. Higher white matter integrity was also associated with fewer reported neurobehavioral symptoms. The findings provide evidence for a complex interplay of ongoing neuroinflammatory processes, white matter integrity, symptomology, and cognitive function in chronic mild-to-moderate TBI. The results underscore the importance of considering both structural brain changes and systemic responses in understanding the long-term effects of TBI. The observed correlations between cognitive deficits, white matter disruptions, and biomarker profiles suggest potential avenues for targeted interventions aimed at mitigating these effects in TBI patients.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484689","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":"Cardiovascular and Locomotor Recovery Following Hindlimb Muscle Stretching of Rodents with a Clinically Relevant Model of Spinal Cord Injury.","authors":"Morgan Forston, Greta Cesarz, Danni Wood, Alice Shum-Siu, David Magnuson","doi":"10.1089/neu.2024.0349","DOIUrl":"https://doi.org/10.1089/neu.2024.0349","url":null,"abstract":"<p><p>Physical therapy stretching remains one of the most prevalent therapies for patients with spinal cord injury (SCI); however, we have previously shown that daily hindlimb muscle stretching of rats following a T10 SCI significantly disrupts their hindlimb locomotor function, likely through maladaptive sprouting of nociceptive afferents and modulation of lumbar spinal circuitry. Despite these clinically significant findings, mid-thoracic contusion models do not represent a majority of clinical injuries and are not effective for modeling the loss of cardiovascular control and autonomic complications that patients with higher level SCI experience. Therefore, the objective of the current study was to examine the effects of hindlimb stretching on the locomotor and cardiovascular function of rats with a T2 SCI. Twenty-six female Sprague-Dawley rats received a moderate T2 contusion (25 g/cm) and were divided into SCI Control (<i>n</i> = 14) and Stretched (<i>n</i> = 12) groups. Our daily hindlimb stretching protocol was initiated at week 5 post-SCI and administered 5 days/week for 4 weeks before a portion of the animals from each group were euthanized. The remaining animals (Control: <i>n</i> = 8, Stretched: <i>n</i> = 6) recovered for 3 weeks before euthanasia. Locomotor function was assessed using the Basso, Beattie and Bresnahan Open Field Locomotor Scale and kinematic gait analysis. Additionally, cardiovascular indices were collected using echocardiography at baseline, pre-stretching, post-stretching, and post-recovery timepoints. Four weeks of daily stretching led to transient disruption of locomotor function as well as reduced overnight activity followed by robust improvements in locomotion once stretching was no longer administered. Although stretching did not appear to have a dramatic effect on cardiovascular indices, both groups displayed significant changes over time in cardiac output and stroke volume. Furthermore, immunohistochemistry staining revealed that stretching did not exacerbate Calcitonin Gene-Related Protein (CGRP⁺) nociceptor sprouting in the lumbar dorsal horn, contrary to the effects we have shown in T10 stretched animals. Overall, these results indicate that hindlimb stretching following a high-thoracic SCI does not appear to aberrantly modulate lumbar spinal circuitry as has been shown in low thoracic injuries. Additionally, stretching combined with a T2 SCI does not result in cardiovascular dysfunction, although future work must be conducted to determine whether stretching triggers autonomic events and maladaptive plasticity near the spinal lesion.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302248","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 Polytrauma Clinical Triad Among Women with a History of Intimate Partner Violence.","authors":"Sharon E Leong, T K Logan, Christal L Badour, Justin E Karr","doi":"10.1089/neu.2025.0064","DOIUrl":"https://doi.org/10.1089/neu.2025.0064","url":null,"abstract":"<p><p>Women with a history of intimate partner violence (IPV) are at risk for traumatic brain injury (TBI) with persistent neurobehavioral symptoms, post-traumatic stress disorder (PTSD), and chronic pain, which, together, characterize the polytrauma clinical triad. Among predominantly male Veteran samples, research has suggested that the triad may exacerbate health problems, compared with the presence of any component of the triad alone. The current study is the first to explore the polytrauma clinical triad among a sample of cisgender women who have experienced IPV (<i>N</i> = 198; <i>M</i> = 39.6 years old, <i>SD</i> = 11.9; 83.3% White, 7.1% Hispanic; 59.1% college-educated). Compared with participants without TBI history, participants with IPV-related TBI had higher rates of chronic pain (43.8% vs. 29.0%, <i>p</i> = 0.045, odds ratio [<i>OR</i>] = 1.87 [95% confidence interval: 1.01, 3.43]), PTSD with chronic pain (19.0% vs. 6.5%, <i>p</i> = 0.009, <i>OR</i> = 3.84 [1.41, 10.46]), neurobehavioral symptoms with chronic pain (40.0% vs. 22.6%, <i>p</i> = 0.030, <i>OR</i> = 2.01 [1.07, 3.79]), and the polytrauma clinical triad (19.0% vs. 6.5%, <i>p</i> = 0.009, <i>OR</i> = 3.84 [1.41, 10.46]), after adjusting for age and education. After controlling for IPV severity, however, there were no statistically significant group differences, suggesting that IPV severity may be closely linked to both risk of TBI and elevated symptomatology associated with the polytrauma clinical triad. Additionally, as the number of lifetime TBIs increased, the odds of having chronic pain (<i>p</i> = 0.011, <i>OR</i> = 1.17 [1.04, 1.33]) and chronic pain with concurrent neurobehavioral symptoms (<i>p</i> = 0.007, <i>OR</i> = 1.05 [1.05, 1.34]) also increased. These findings suggest that, especially when comorbid with IPV-related TBI, chronic pain may be a priority treatment target among individuals with a history of IPV. Considering that women with a history of IPV often experience concurrent health conditions, multicomponent interventions that address each condition within the polytrauma clinical triad may benefit this population.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285024","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":"Repeated Exposures to Air Travel-Relevant Hypobaria Induce Anxiety-Like Behavior and Alter Functional Connectivity and White Matter Integrity in a Ferret Model of Traumatic Brain Injury.","authors":"Li Jiang, Molly J Goodfellow, Su Xu, Amanda Hrdlick, Boris Piskoun, Julie L Proctor, Xiao Liang, Steven Roys, Xin Li, Rao P Gullapalli, Ulrich H Leiste, William Fourney, Jody C Cantu, Catriona H T Miller, Jiachen Zhuo, Gary Fiskum","doi":"10.1089/neu.2024.0531","DOIUrl":"https://doi.org/10.1089/neu.2024.0531","url":null,"abstract":"<p><p>Under-vehicle blast (UVB) caused by landmine detonation induces a distinct traumatic brain injury (TBI) and can be accompanied by head impact. Injured soldiers often undergo multiple flights after injury to access medical care and return to duty. Previous work has shown that low air pressure during air travel (hypobaria [HB]) exacerbates neurological injury, but the effects of one or more HB exposures on chronic brain injury are unknown. We hypothesized that multiple HB exposures after TBI would result in worse outcomes than 0-1 exposures. Sedated male ferrets underwent UVB and controlled cortical impact (CCI) under anesthesia (BCCI), followed by zero (normobaria [BCCI + NB]), one (BCCI + 1HB), or five (BCCI + 5HB) 6-h HB exposure(s) over 6 months post-injury or remained experimentally naïve. Anxiety-like behavior was assessed with the Open Field at 6 months post-injury. Ferrets also underwent T₂-weighted (T2w), resting-state functional magnetic resonance imaging, and diffusion-weighted imaging scans at pre-injury baseline and 6 months post-injury under anesthesia. Relative to naïve, BCCI + 5HB animals expressed significantly more anxiety-like behavior. Region of interest (ROI)-to-ROI functional connectivity (FC) analysis was conducted to evaluate FC changes within the anxiety network. ROI-based diffusion tensor and kurtosis imaging modeling was conducted to evaluate the white matter (WM) integrity of major anxiety-associated WM tracts. Results indicated increased FC between prefrontal cortex, amygdala, and hippocampus and decreased fractional anisotropy and mean kurtosis in cerebral WM, corpus callosum, cingulum, and fornix WM tracts when comparing BCCI + 5HB with all other groups. Together, these suggest that multiple HB exposures after BCCI exacerbate changes in neurological activity in the anxiety regulation brain network, as well as structural damage in the anxiety-associated WM tracts. Our findings demonstrate that air travel after TBI, particularly multiple flights, can have a chronic negative impact on brain structure and function.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285022","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1089/neu.2024.0232","url":null,"abstract":"&lt;p&gt;&lt;p&gt;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 (&lt;i&gt;p&lt;/i&gt;&lt;sub&gt;treatment*sex_interaction&lt;/sub&gt; &lt; 0.0001) and rotarod latency (&lt;i&gt;p&lt;/i&gt;&lt;sub&gt;treatment*sex_interaction&lt;/sub&gt; = 0.016, revolutions per minute, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;treatment*sex_interaction&lt;/sub&gt; = 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&gt;females, all &lt;i&gt;p&lt;/i&gt; &lt; 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 &lt;i&gt;p&lt;/i&gt; &lt; 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 (&lt;i&gt;p&lt;/i&gt;&lt;sub&gt;72h&lt;/sub&gt; &lt; 0.01, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;21d&lt;/sub&gt; &lt; 0.001). GLI increased DG SOX2 in females (&lt;i&gt;p&lt;/i&gt;&lt;sub&gt;72h&lt;/sub&gt; &lt; 0.05, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;21d&lt;/sub&gt; &lt; 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 (&lt;i&gt;p&lt;/i&gt; = 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":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcranial Photobiomodulation Improves Cognitive Function, Post-Concussion, and PTSD Symptoms in Mild Traumatic Brain Injury.","authors":"Tsz-Lok Lee, David Yuen-Chung Chan, Danny Tat-Ming Chan, Mei-Chun Cheung, David Ho-Keung Shum, Agnes Sui-Yin Chan","doi":"10.1089/neu.2025.0048","DOIUrl":"https://doi.org/10.1089/neu.2025.0048","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) occurs in millions of people globally each year, with mild TBI (mTBI) representing over 90% of cases. Despite the common assumption of full recovery, significant disturbances persist in many patients with mTBI, including cognitive deficit, headache, dizziness, sleep problems, and symptoms of post-traumatic stress disorder (PTSD). Given that effective treatment is still scarce, the present study investigated the efficacy of transcranial photobiomodulation (tPBM) as an intervention for improving these sequelae in patients with mTBI. In this randomized placebo-controlled trial, 17 patients with mTBI were recruited. Participants were randomized to receive both real and sham tPBM conditions with a counterbalanced order, with a 1-week washout between interventions. Assessments were conducted at baseline, after real tPBM, and after sham tPBM. These included neuropsychological tests, measurements of oxygenated hemoglobin using functional near-infrared spectroscopy during a visual working memory task, and self-rated questionnaires assessing sleep quality, physical post-concussion symptoms, pain intensity, and PTSD symptoms. Compared with the baseline, participants demonstrated significant improvements. After receiving tPBM, patients showed enhanced cognitive efficiency, as evidenced by improved visual working memory performance, better learning in verbal memory tests, improved subjective sleep quality, fewer physical post-concussion symptoms, reduced pain intensity, and decreased PTSD symptoms. In contrast, no significant improvement was observed after patients received the sham tPBM. In addition, the statistically significant improvement in behavioral symptoms also reached the minimal clinically important difference, suggesting clinical significance. These findings support the potential of tPBM as a safe, non-invasive clinical intervention for cognitive deficits and associated symptoms in mTBI. Further exploration is encouraged to evaluate tPBM as a rehabilitation strategy for enhancing recovery in TBI patients.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248345","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}