Journal of neurotrauma最新文献

{"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":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","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}

{"title":"Evolution of Real-World Clinical Practice in Time to Surgery Following Thoracolumbar Spinal Cord Injury: An Observational Study of North American Trauma Centers from 2010 to 2020.","authors":"Ahmad Essa, Armaan K Malhotra, Husain Shakil, Jetan Badhiwala, Avery B Nathens, Eva Y Yuan, Yingshi He, Andrew S Jack, Francois Mathieu, Jefferson R Wilson, Christopher D Witiw","doi":"10.1089/neu.2024.0125","DOIUrl":"10.1089/neu.2024.0125","url":null,"abstract":"<p><p>This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. Descriptive plots and a multivariable Poisson regression model with time to spine surgery as the primary outcome were constructed. This study included 4350 adult patients with complete SCI surgically treated across 449 trauma centers. Within this group, 3978 (91.4%) patients were diagnosed with thoracic SCI and 372 (8.6%) patients were diagnosed with lumbar SCI. The overall mean time to surgery was 31.6 h (±34.1). Early surgery (≤24 h) was performed in 2599 patients (59.7%). An estimated annual reduction of 1.6 h in time to surgery was demonstrated over the study period, starting initially at a mean of 47.6 h (±40.6) in 2010, and reaching a mean of 25.3 h (±30) in 2020. Multivariable Poisson regression adjusting for patient, injury, and institution confounders, demonstrated a significant decrease in time to surgery by 5% per year over the study period (incidence rate ratios [IRR] = 0.95, 95% confidence interval [CI]: 0.93-0.96). Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589614","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":"Time to Surgery Following Complete Cervical Spinal Cord Injury: Evolution of Clinical Practice Patterns Over a Decade from 2010 to 2020 Across North American Trauma Centers.","authors":"Ahmad Essa, Husain Shakil, Armaan K Malhotra, Jetan Badhiwala, Eva Y Yuan, Yingshi He, Andrew S Jack, Francois Mathieu, Avery B Nathens, Jefferson R Wilson, Christopher D Witiw","doi":"10.1089/neu.2024.0025","DOIUrl":"https://doi.org/10.1089/neu.2024.0025","url":null,"abstract":"<p><p>This study aims to quantify the change in time to surgery for treatment of complete traumatic cervical spinal cord injury (SCI) patients in American College of Surgeons accredited trauma centers across North America over the last decade (2010-2020). This multi-center retrospective observational cohort study used data from the Trauma Quality Improvement Program from 2010 to 2020. All surgically treated patients with complete traumatic cervical SCI were included. Primary outcome was time to spine surgery from treating hospital arrival in hours. Both descriptive statistics and a multi-variable Poisson regression model clustering standard of errors by each included trauma center were used to evaluate and quantify the annual change in time to surgical intervention. The study included 6855 complete traumatic cervical SCI patients managed across 484 trauma centers in North America. Median time to spine surgery was 14.6 h. A total of 4618 patients (67.3%) underwent surgical intervention within 24 h from hospital arrival. From 2010 to 2020, median time to surgery decreased by an average 0.6 h (±0.15) per year. A multi-variable adjusted model for time to surgery demonstrated a significant downward annual reduction of 5% in time to surgery between the years 2010 and 2020 (Incidence rate ratio = 0.95; 95% Confidence Interval: 0.93-0.96). This study provides compelling real-world based quantification of the change in time to surgical intervention following traumatic cervical SCI. A significant decreasing annual trend pertaining to surgical timing across trauma centers in North America over the past decade was demonstrated.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583197","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":"Is There an Optimal Time Window of Placement of Intracranial Pressure (ICP) Monitor for Elderly Patients With Severe Traumatic Brain Injury? An 11-Year Institutional Cohort Study With Restricted Cubic Spline Analysis.","authors":"Yuan Wang, Shaochun Guo, Peigang Ji, Ruili Han, Na Wang, Jinghui Liu, Fan Chen, Yulong Zhai, Yue Wang, Yang Jiao, Wenjian Zhao, Chao Fan, Yanrong Xue, Liang Qu, GuoDong Gao, Yan Qu, Liang Wang","doi":"10.1089/neu.2023.0610","DOIUrl":"10.1089/neu.2023.0610","url":null,"abstract":"<p><p>Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2363-2376"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996488","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":"Intravenous Administration of Anti-CD47 Antibody Augments Hematoma Clearance, Mitigates Acute Neuropathology, and Improves Cognitive Function in a Rat Model of Penetrating Traumatic Brain Injury.","authors":"Ping Wang, Xiaofang Yang, Fangzhou Yang, Katherine Cardiff, Melonie Houchins, Noemy Carballo, Deborah A Shear, Anke H Scultetus, Zachary S Bailey","doi":"10.1089/neu.2024.0047","DOIUrl":"10.1089/neu.2024.0047","url":null,"abstract":"<p><p>Traumatic brain injury (TBI)-induced intracerebral hematoma is a major driver of secondary injury pathology such as neuroinflammation, cerebral edema, neurotoxicity, and blood-brain barrier dysfunction, which contribute to neuronal loss, motor deficits, and cognitive impairment. Cluster of differentiation 47 (CD47) is an antiphagocytic cell surface protein inhibiting hematoma clearance. This study was designed to evaluate the safety and efficacy of blockade of CD47 via intravenous (i.v.) administration of anti-CD47 antibodies following penetrating ballistic-like brain injury (PBBI) with significant traumatic intracerebral hemorrhage (tICH). The pharmacokinetic (PK) profile of the anti-CD47 antibody elicited that antibody concentration decayed over 7 days post-administration. Blood tests and necropsy analysis indicated no severe adverse events following treatment. Cerebral hemoglobin levels were significantly increased after injury, however, anti-CD47 antibody administration at 0.1 mg/kg resulted in a significant reduction in cerebral hemoglobin levels at 72 h post-administration, indicating augmentation of hematoma clearance. Immunohistochemistry assessment of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) demonstrated a significant reduction of GFAP levels in the lesion core and peri-lesional area. Based on these analyses, the optimal dose was identified as 0.1 mg/kg. Lesion volume showed a reduction following treatment. Rotarod testing revealed significant motor deficits in all injured groups but no significant therapeutic benefits. Spatial learning performance revealed significant deficits in all injured groups, which were significantly improved by the last testing day. Anti-CD47 antibody treated rats showed significantly improved attention deficits, but not retention scores. These results provide preliminary evidence that blockade of CD47 using i.v. administration of anti-CD47 antibodies may serve as a potential therapeutic for TBI with ICH.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2413-2427"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317564","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":"Synaptic Plasticity in the Injured Brain Depends on the Temporal Pattern of Stimulation.","authors":"Quentin S Fischer, Djanenkhodja Kalikulov, Gonzalo Viana Di Prisco, Carrie A Williams, Philip R Baldwin, Michael J Friedlander","doi":"10.1089/neu.2024.0129","DOIUrl":"10.1089/neu.2024.0129","url":null,"abstract":"<p><p>Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naive), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naive or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2455-2477"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179913","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":"Impact of Sex and Pubertal Development on Anxiety in Adolescents After Concussion.","authors":"Dean Gomes, Shawn Eagle, Bindal Mehmel, Ted Albrecht, Amelia Versace, João Paulo Lima Santos, Alicia Trbovich, Richelle Stiffler, Laramie Martinez, Cyndi L Holland, Aaron J Zynda, Michael W Collins, Anthony P Kontos","doi":"10.1089/neu.2023.0132","DOIUrl":"10.1089/neu.2023.0132","url":null,"abstract":"<p><p>Concussion often results in psychological symptoms, including anxiety. Post-concussion anxiety has been well documented, although much of this research has focused on collegiate athletes. The purpose of this study was to compare (1) anxiety symptoms in concussed and healthy controls over time and (2) to explore sex differences in post-concussion anxiety within the context of pubertal development. Participants (N = 126, mean age = 15.1 years old), including concussed (<i>n</i> = 86) and healthy adolescents (<i>n</i> = 40), completed the Pubertal Development Scale (PDS) and the Screen for Child Anxiety and Related Disorders (SCARED-C). The concussed groups completed SCARED-C at three visits (<u><</u>10 days, 4 weeks, 3 months). Results of an analysis of covariance (ANCOVA) and multi-variate analysis of covariance (MANCOVA) found concussed adolescents reported higher SCARED-C total, generalized, and panic anxiety scores than healthy controls, after controlling for sex, age, and PDS score (PDSS). A three-way mixed ANCOVA examined the effects of sex, PDSS, time, and their interaction on SCARED-C total score in concussed adolescents while controlling for age. There was a significant three-way interaction between sex, age, and PDSS on SCARED-C total score while controlling for age. Overall, we observed increased anxiety in concussed adolescents, compared with controls, as well as greater post-concussion anxiety reported by females compared with males, including within PDSS groups. Concussion providers should be prepared to receive training to administer well-validated measures of psychopathology and should consider that female adolescents, compared with males, regardless of pubertal development, may be at greater risk for post-concussion anxiety.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2385-2394"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972245","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 Injury Progression in Acute Blast-Induced Mild Traumatic Brain Injury in Rats Reflected by Diffusion Tensor Imaging and Immunohistochemical Examination.","authors":"Yalan Liao, Yang Li, Li Wang, Ye Zhang, Linqiong Sang, Qiannan Wang, Pengyue Li, Kunlin Xiong, Mingguo Qiu, Jingna Zhang","doi":"10.1089/neu.2023.0435","DOIUrl":"10.1089/neu.2023.0435","url":null,"abstract":"<p><p>Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2478-2492"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321007","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":"Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.","authors":"Kengo Nishimura, Juliana Sanchez-Molano, Nadine Kerr, Yelena Pressman, Risset Silvera, Aisha Khan, Shyam Gajavelli, Helen M Bramlett, W Dalton Dietrich","doi":"10.1089/neu.2023.0650","DOIUrl":"10.1089/neu.2023.0650","url":null,"abstract":"<p><p>There is a growing body of evidence that the delivery of cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord injury and improve outcomes. Exosomes are nanometer-sized vesicles that are released by Schwann cells and may have neuroprotective effects by reducing post-traumatic inflammatory processes as well as promoting tissue healing and functional recovery. The purpose of this study was to evaluate the beneficial effects of human Schwann-cell exosomes (hSC-Exos) in a severe model of penetrating ballistic-like brain injury (PBBI) in rats and investigate effects on multiple outcomes. Human Schwann cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction and purification steps approved by the Food and Drug Administration for an expanded access single ALS patient Investigational New Drug. Anesthetized male Sprague-Dawley rats (280-350g) underwent PBBI surgery or Sham procedures and, starting 30 min after injury, received either a dose of hSC-Exos or phosphate-buffered saline through the jugular vein. At 48h after PBBI, flow cytometry analysis of cortical tissue revealed that hSC-Exos administration reduced the number of activated microglia and levels of caspase-1, a marker of inflammasome activation. Neuropathological analysis at 21 days showed that hSC-Exos treatment after PBBI significantly reduced overall contusion volume and decreased the frequency of Iba-1 positive activated and amoeboid microglia by immunocytochemical analysis. This study revealed that the systemic administration of hSC-Exos is neuroprotective in a model of severe TBI and reduces secondary inflammatory injury mechanisms and histopathological damage. The administration of hSC-Exos represents a clinically relevant cell-based therapy to limit the detrimental effects of neurotrauma or other progressive neurological injuries by impacting multiple pathophysiological events and promoting neurological recovery.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2395-2412"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039648","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":"Response to McEvoy et al., 2023, Cumulative Blast Exposure Estimate Model for Special Operations Forces Combat Soldiers.","authors":"Sherri Tschida, Emily Thomas","doi":"10.1089/neu.2024.0249","DOIUrl":"10.1089/neu.2024.0249","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2493-2494"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759243","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}