Journal of neurotrauma最新文献

{"title":"Response to Thompson and Moore.","authors":"Justin Maldonado, Jason H Huang, Ed W Childs, Binu Tharakan","doi":"10.1089/neu.2023.0622","DOIUrl":"https://doi.org/10.1089/neu.2023.0622","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066105","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":"Attenuation of Blood-Brain Barrier Disruption in Traumatic Brain Injury via Inhibition of NKCC1 Cotransporter: Insights into the NF-κB/NLRP3 Signaling Pathway.","authors":"Zehan Zhang, Hui Wang, Bingyan Tao, Xudong Shi, Guilin Chen, Hengchao Ma, Ruiyun Peng, Jun Zhang","doi":"10.1089/neu.2023.0580","DOIUrl":"https://doi.org/10.1089/neu.2023.0580","url":null,"abstract":"<p><p>Following traumatic brain injury (TBI), inhibition of the Na⁺-K⁺-Cl^- cotransporter1 (NKCC1) has been observed to alleviate damage to the blood-brain barrier (BBB). However, the underlying mechanism for this effect remains unclear. This study aimed to investigate the mechanisms by which inhibiting the NKCC1 attenuates disruption of BBB integrity in TBI. The TBI model was induced in C57BL/6 mice through a controlled cortical impact device, and an <i>in vitro</i> BBB model was established using Transwell chambers. Western blot (WB) analysis was used to evaluate NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor-kappaB (NF-κB) pathway proteins. Flow cytometry and transendothelial electrical resistance (TEER) were employed to assess endothelial cell apoptosis levels and BBB integrity. ELISA was utilized to measure cytokines interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence techniques were used to evaluate protein levels and the nuclear translocation of the rela (p65) subunit. The Evans blue dye leakage assay and the brain wet-dry weight method were utilized to assess BBB integrity and brain swelling. Inhibition of NKCC1 reduced the level of NLRP3 inflammasome and the secretion of IL-1β and MMP-9 in microglia. Additionally, NKCC1 inhibition suppressed the activation of the NF-κB signaling pathway, which in turn decreased the level of NLRP3 inflammasome. The presence of NLRP3 inflammasome in BV2 cells led to compromised BBB integrity within an inflammatory milieu. Following TBI, an upregulation of NLRP3 inflammasome was observed in microglia, astrocytes, vascular endothelial cells, and neurons. Furthermore, inhibiting NKCC1 resulted in a decrease in the positive rate of NLRP3 inflammasome in microglia and the levels of inflammatory cytokines IL-1β and MMP-9 after TBI, which correlated with BBB damage and the development of cerebral edema. These findings demonstrate that the suppression of the NKCC1 cotransporter protein alleviates BBB disruption through the NF-κB/NLRP3 signaling pathway following TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066098","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":"Human Neural Stem Cell Therapy for Traumatic Brain Injury-A Systematic Review of Pre-Clinical Studies.","authors":"Sarah L Schantz, Kylee J Duberstein, Erin E Kaiser, Franklin D West","doi":"10.1089/neu.2024.0544","DOIUrl":"https://doi.org/10.1089/neu.2024.0544","url":null,"abstract":"<p><p>Human neural stem cells (hNSCs) possess significant therapeutic potential for the treatment of traumatic brain injury (TBI), a leading cause of global death and disability. Recent pre-clinical studies have shown that hNSCs reduce tissue damage and promote functional recovery through neuroprotective and regenerative signaling and cell replacement. Yet the overall efficacy of hNSCs for TBI indications remains unclear. Therefore, this systematic review aims to evaluate hNSC interventions compared with controls in pre-clinical TBI models. Through this process, variations in hNSC administration protocols were consolidated, and key knowledge gaps were identified. Meta-analysis was applied to primary outcomes of lesion volume, Morris Water Maze (MWM) performance, modified Neurological Severity Scores (mNSS), and the rotarod task. Narrative review of secondary outcomes included hNSC survival and differentiation, endogenous neuron survival, axonal injury, and inflammation. Overall, hNSC intervention reduced lesion volume, enhanced MWM performance, and led to trending decreases in acute and chronic neurological deficits at acute and chronic time points. These results suggest hNSCs demonstrate clear efficacy in pre-clinical TBI models. However, further studies are needed to address key questions regarding optimal hNSC administration (e.g., dosing, treatment window) and underlying mechanisms of action prior to progressing to human clinical trials.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032930","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":"Sex Differences in Neurological Outcome at 6 and 12 Months Following Severe Traumatic Brain Injury. An Observational Analysis of the OXY-TC Trial.","authors":"Jean-Francois Payen, Antoine Vilotitch, Tobias Gauss, Anais Adolle, Jean-Luc Bosson, Pierre Bouzat","doi":"10.1089/neu.2024.0390","DOIUrl":"https://doi.org/10.1089/neu.2024.0390","url":null,"abstract":"<p><p>The effect of sex in outcomes after severe traumatic brain injury (TBI) remains uncertain. We explored whether outcomes differed between women and men after standardized care management during the first 5 days in the intensive care unit (ICU). This study was an observational analysis of the OXY-TC multicenter randomized clinical trial between June 15, 2016 and April 17, 2021. Recruited patients had a pre-hospital Glasgow Coma Scale (GCS) score of 3-8, mechanical ventilation, and intracranial pressure (ICP) with or without brain tissue oxygen pressure (PbtO₂) monitoring. Objectives were to maintain ICP at 20 mmHg or below and PbtO2 above 20 mmHg at all times. The primary end-point was the proportion of women and men with poor outcomes at 6 months, corresponding to an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability). Of 318 randomized patients, 200 men and 71 women were analyzed. They were comparable in age, comorbidities, and initial injury severity scores. However, women had larger doses of ICP as the proportion of monitoring time of ICP above 20 mmHg 8% (3-18; median, interquartile range) versus 3% (1-10), respectively (<i>p</i> = 0.002). They required more often at least one tier-3 treatment, i.e., barbiturate coma and therapeutic hypothermia, for refractory intracranial hypertension during the first 5 days in the ICU: 33/68 (48%) versus 60/193 (31%), respectively (<i>p</i> = 0.012). At 6 months, the proportion of women with GOSE 1-4 was significantly higher than men: 48/71 (68%) versus 94/200 (47%), respectively (odds ratio 2.35 [1.33-4.16]; <i>p</i> = 0.003]. Similar differences were found using Disability Rating Scale and Functional Independence Measure at 6 and 12 months, and GOSE at 12 months. Sex differences in neurological outcomes persisted after adjustment for other determinants of outcome such as age, initial GCS score, and dose of ICP during the 5-day monitoring. In conclusion, women sustained more severe ICP and required more active treatment, both of which would explain a worse outcome after severe TBI. Prospective research is required to confirm these findings and identify possible mechanisms. Trial registration: ClinicalTrials.gov Identifier NCT02754063 (April 28, 2016).</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023616","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":"Translational Outcomes Project in Neurotrauma (TOP-NT) Pre-Clinical Consortium Study: A Synopsis.","authors":"Hannah L Radabaugh, Neil G Harris, Ina B Wanner, Mark P Burns, Joseph T McCabe, Alexandru V Korotcov, Bernard J Dardzinski, Jinyuan Zhou, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Babak Moghadas, Adnan Bibic, Marcelo Febo, Firas H Kobeissy, Jiepei Zhu, Richard Rubenstein, Jiamei Hou, Prodip K Bose, Seza Apiliogullari, Michael S Beattie, Jacqueline C Bresnahan, Susanna Rosi, J Russell Huie, Adam R Ferguson, Kevin K W Wang","doi":"10.1089/neu.2023.0654","DOIUrl":"https://doi.org/10.1089/neu.2023.0654","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) has long been a leading cause of death and disability, yet research has failed to successfully translate findings from the pre-clinical, animal setting into the clinic. One factor that contributes significantly to this struggle is the heterogeneity observed in the clinical setting where patients present with injuries of varying types, severities, and comorbidities. Modeling this highly varied population in the laboratory remains challenging. Given feasibility constraints, individual laboratories often focus on single injury types and are limited to an abridged set of outcome measures. Furthermore, laboratories tend to use different injury or outcome methodologies from one another, making it difficult to compare studies and identify which pre-clinical findings may be best suited for clinical translation. The NINDS-funded Translational Outcomes Project in Neurotrauma (TOP-NT) is a multi-site consortium designed to address the reproducibility, rigor, and transparency of pre-clinical development and validation of clinically relevant biomarkers for TBI. The current overview article provides a detailed description of the infrastructure and strategic approach undertaken by the consortium. We outline the TOP-NT strategy to address three goals: (1) selection and cross-center validation of biomarker tools, (2) development and population of a data infrastructure to allow for the sharing and reuse of pre-clinical, animal research following findable, accessible, interoperable, and reusable data guidelines, and (3) demonstration of feasibility, reproducibility, and transparency in conducting a multi-center, pre-clinical research trial for TBI biomarker development. The synthesized scientific analysis and results of the TOP-NT efforts will be the topic of future articles.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023621","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":"Prospective Harmonization, Common Data Elements, and Sharing Strategies for Multicenter Pre-Clinical Traumatic Brain Injury Research in the Translational Outcomes Project in Neurotrauma Consortium.","authors":"Ina-Beate Wanner, Joseph T McCabe, J Russell Huie, Neil G Harris, Afshin Paydar, Chloe McMann-Chapman, Anthony Tobar, Alexandru Korotcov, Mark P Burns, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Jonathan Tong, Jinyuan Zhou, Lex Maliga Davis, Hannah L Radabaugh, Adam R Ferguson, Timothy E Van Meter, Marcelo Febo, Prodip Bose, Kevin K Wang, Firas Kobeissy, Seza Apiliogullari, Jiepei Zhu, Richard Rubenstein, Hibah O Awwad","doi":"10.1089/neu.2023.0653","DOIUrl":"https://doi.org/10.1089/neu.2023.0653","url":null,"abstract":"<p><p>Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing and validating noninvasive TBI assessment tools through team science. Here, we present practical approaches for harmonization of TBI research across five centers providing needed vocabulary and structure to achieve centralized data organization and use. This includes data sharing as an essential step that enables validating data between domains, evaluating reproducibility between sites, and performing multimodal analyses. As part of this process, TOP-NT (1) produced a library of TBI-relevant standard operating procedures to coordinate workflow, (2) aligned 481 pre-clinical and clinical common data elements (CDEs), and (3) generated 272 new pre-clinical TBI CDEs. This consortium then (4) connected diverse data types to validate assessments across domains and to allow multivariable TBI phenotyping. Lastly, TOP-NT (5) specified technical quality controls for pre-clinical studies. These harmonization tools can facilitate reproducibility in team science, help distinguish a wide injury spectrum from technical variability, apply quality-controls, and ease higher level data analyses. TOP-NT uses three rat TBI models across four sites. Each site collects primary outcome measures, including magnetic resonance imaging (MRI) protocols and blood biomarkers of neuronal and glial injury, validated by histopathology and behavioral outcomes. Collected data are organized using the 481 TOP-NT pre-clinical CDEs, covering surgical, behavioral, biomarker, MRI, and quantitative histopathological methods. We report data curation steps suited for data storage using the Open Data Commons for TBI as a centralized data repository, allowing unbiased cross-site analysis. This approach leads to introducing a higher level, syndromic understanding of TBI signatures. TOP-NT authors outline a semantic and structural framework suggesting strategies for robust pre-clinical research in multicenter trials to improve translatability for TBI assessments. [Figure: see text].</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006954","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":"Priority Clinical Actions for Outpatient Management of Nonhospitalized Traumatic Brain Injury.","authors":"Noah D Silverberg, Kathy Lee, Ana Mikolić, Mark T Bayley, David L Brody, E Wesley Ely, Joseph T Giacino, Cathra Halabi, Flora M Hammond, Daniel A Ignacio, Caterina Mosti, Joukje van der Naalt, Monique R Pappadis, Olli Tenovuo, Vincent Y Wang, Monica Verduzco-Gutierrez, Geoffrey T Manley","doi":"10.1089/neu.2024.0414","DOIUrl":"https://doi.org/10.1089/neu.2024.0414","url":null,"abstract":"<p><p>Outpatient care following nonhospitalized traumatic brain injury (TBI) is variable, and often sparse. The National Academies of Sciences, Engineering, and Medicine's 2022 report on <i>Traumatic Brain Injury: A Roadmap for Accelerating Progress</i> highlighted the need to improve the consistency and quality of TBI care in the community. In response, the present study aimed to identify existing evidence-based guidance and specific clinical actions over the days to months following nonhospitalized TBI that should be prioritized for implementation in primary care. In systematic literature searches, 17 clinical practice guidelines met our eligibility criteria and an additional expert consensus statement was considered highly relevant. We extracted 73 topics covered by one or more existing clinical practice guidelines. After removing redundant and out-of-scope topics, those deemed essential (not requiring prioritization), 42 topics were subjected to a prioritization exercise. Experts from the author group (<i>n</i> = 14), people with lived experience (<i>n</i> = 112), and clinicians in the community (<i>n</i> = 99) selected and ranked topics they considered most important. There were areas of agreement (e.g., early education was ranked highly by all groups) and discordance (e.g., people with lived experience perceived diagnostic tests/investigations as more important than the other groups). We synthesized the prioritization survey results into a top-10 list of the highest priority clinical actions. This list will inform implementation efforts aimed at improving post-acute care for nonhospitalized TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932036","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 and Cognitive Consequences of Spreading Depolarizations: A Translational Scoping Review.","authors":"Faith V Best, Jed A Hartings, Yara Alfawares, Steve C Danzer, Laura B Ngwenya","doi":"10.1089/neu.2024.0118","DOIUrl":"10.1089/neu.2024.0118","url":null,"abstract":"<p><p>Spreading depolarizations (SDs) are self-propagating waves of mass depolarization that cause silencing of brain activity and have the potential to impact brain function and behavior. In the eight decades following their initial discovery in 1944, numerous publications have studied the cellular and molecular underpinning of SDs, but fewer have focused on the impact of SDs on behavior and cognition. It is now known that SDs occur in more than 60% of patients with moderate-to-severe traumatic brain injury (TBI), and their presence is associated with poor 6-month outcomes. Since cognitive dysfunction is a key component of TBI pathology and recovery, understanding the impact of SDs on behavior and cognition is an important step in developing diagnostic and therapeutic approaches. This study summarizes the known behavioral and cognitive consequences of SDs based on historical studies on awake animals, recent experimental paradigms, and modern clinical examples. This scoping review showcases our current understanding of the impact of SDs on cognition and behavior and highlights the need for continued research on the consequences of SDs.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1-18"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567096","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":"A Mouse Model of Temporal Lobe Contusion.","authors":"J Marc Simard, Cigdem Tosun, Orest Tsymbalyuk, Mitchell Moyer, Kaspar Keledjian, Natalya Tsymbalyuk, Adedayo Olaniran, Madison Evans, Jenna Langbein, Ziam Khan, Matthew Kreinbrink, Prajwal Ciryam, Jesse A Stokum, Ruchira M Jha, Alexander Ksendzovsky, Volodymyr Gerzanich","doi":"10.1089/neu.2024.0242","DOIUrl":"10.1089/neu.2024.0242","url":null,"abstract":"<p><p>Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, \"computed tomography-positive,\" that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"143-160"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289464","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":"Validating the Brain Injury Guidelines in a Pediatric Population with Mild Traumatic Brain Injury and Intracranial Injury at a Level I Trauma Center.","authors":"Nina Yu, Jose Castillo, Jonathan E Kohler, James P Marcin, Daniel K Nishijima, Jonathan Mo, Lori Kennedy, Kiarash Shahlaie, Marike Zwienenberg","doi":"10.1089/neu.2024.0130","DOIUrl":"10.1089/neu.2024.0130","url":null,"abstract":"<p><p>Children with mild traumatic brain injury (mTBI) and intracranial injury (ICI) often receive unnecessary imaging and hospital admission, leading to avoidable burdens on patients and health systems. While most of these patients do not develop critical neurological injuries, identifying those at risk would allow for a more optimal determination of the appropriate level of initial emergency care. The Brain Injury Guidelines (BIG) were developed as a triage tool to identify adult patients with mTBI and ICI who can benefit from repeat imaging, hospital admission, or neurosurgical consultation. Here, we sought to validate BIG in children at a Level I trauma center and determine if the BIG algorithm can accurately identify which patients with mTBI/ICI have critical neurosurgical injuries. We hypothesize that the BIG can identify critical neurological injuries more accurately than the Glasgow Coma Scale (GCS) alone and that more severe injury according to BIG is associated with worse patient outcome. We retrospectively reviewed TBI admissions at a single center (2017-2023) using an institutional registry. Patients included (0-17 years) had an initial head computerized tomography scan with ICI and a GCS of 14-15. Patients were retrospectively classified into the BIG categories (BIG 1, 2, or 3). Medical records were reviewed to identify clinically important TBI (ciTBI): death, neurological deterioration, neurosurgical intervention, intubation >24 h, or hospital admission >48 h due to TBI. Repeat imaging studies obtained were evaluated for progression of injury. The incidence of clinically important TBI (ciTBI) and imaging progression were recorded and compared across BIG categories. Outcomes were evaluated using the Glasgow Outcome Score Extended (GOS-E) 6 months after injury. Univariable and chi-square tests were used to analyze comparisons. Overall, 804 subjects were included in the analysis of which 551 (68.5%) were transfers. Overall, 175 (21.8%) patients had a BIG 1, 402 (50.0%) a BIG 2, and 227 (28.2%) a BIG 3 injury. CiTBI occurred among 64 (8.0%) patients overall, and in 1 (0.6%), 4 (1.0%), and 59 (26.0%) of the BIG 1, 2, and 3 injuries (<i>p</i> < 0.0001). Progression on repeat imaging associated with neurological decline, neurosurgical intervention or resulting in additional evaluation was noted in 0 (0%), 2 (0.5%), and 41 (18.0%) of the BIG 1, 2, and 3 injuries (<i>p</i> < 0.001). Amongst 471 patients (58.6%) with available 6-month patient outcomes, 98% had a GOS-E ≥5 and no outcome difference between BIG categories was observed. Risk stratification of mild TBI using BIG allowed for reasonable identification of children who subsequently develop ciTBI, suggesting that BIG classification can aid in triage and management of patients who might benefit from neurosurgical consultation, repeat imaging, and potentially transfer to a dedicated trauma center. More severe injury according to BIG was not associated with a worse patient outcome.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"71-81"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589535","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}