Journal of neurotrauma最新文献

{"title":"<i>Response to the Letter to the Editor:</i> \"Comments on 'Acupuncture Treatment for Chronic Post-Traumatic Headache in Individuals with Mild Traumatic Brain Injury: A Pilot Study'\".","authors":"Amanda A Herrmann, Ella A Chrenka, Sophia G Bouwens, Ellie K Tansey, Ayla A Wolf, Kerri W Chung, Marny T Farrell, Samantha J Sherman, Aleta L Svitak, Leah R Hanson","doi":"10.1089/neu.2025.0178","DOIUrl":"https://doi.org/10.1089/neu.2025.0178","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142786","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":"Outcomes and Challenges in Treating Acute Subdural Hematoma in Older Adults with a GCS Score of 3-5: A Nationwide Retrospective Analysis in Korea.","authors":"Ki Seong Eom","doi":"10.1089/neu.2025.0009","DOIUrl":"https://doi.org/10.1089/neu.2025.0009","url":null,"abstract":"<p><p>Traumatic brain injury with a Glasgow Coma Scale (GCS) score of 3-5 is characterized by severe injury, poor prognosis, and low survival rates. Deciding between aggressive neurosurgery and treatment discontinuation is challenging among older adults. This study analyzed the characteristics, treatment, and outcomes of acute subdural hematoma (ASDH) in older adults with a GCS score of 3-5 to assess the benefits of surgery and guide future treatment decisions. We analyzed the data of 205 older adults (aged 65 years or older) with ASDH and a GCS score of 3-5 registered in the Korean Neuro-Trauma Data Bank System from January 2018 to June 2021. The patients were divided into death and survival groups, and the demographic, clinical, and radiological characteristics; treatment methods; mortality rates; and treatment outcomes were analyzed, along with the relationship between variables and mortality. We also compared the Glasgow Outcome Scale-Extended (GOSE) scores and investigated whether surgical treatment affected mortality and good recovery rates according to age. According to the GOSE, 76.1% of patients died, 12.7% survived in a vegetative state, 3.9% had severe disabilities, and only 4.0% showed good recovery. The GCS score at admission was significantly associated with pupil reactivity; Rotterdam computed tomography score; time interval from injury to operation and arrival to operation; treatment; and hospital stay between patients who died and those who survived. Surgical treatment was significantly associated with a lower mortality rate but not with good recovery rates.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120044","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":"Mild Traumatic Brain Injury Impairs Fear Extinction and Network Excitability in the Infralimbic Cortex.","authors":"Catherine E Ubri, Anthony M Farrugia, Akiva S Cohen","doi":"10.1089/neu.2025.0046","DOIUrl":"https://doi.org/10.1089/neu.2025.0046","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with mild TBI (concussions) representing over 80% of cases. Although often considered benign, mild TBI is associated with persistent neuropsychiatric conditions, including post-traumatic stress disorder, anxiety, and depression. A hallmark of these conditions is impaired fear extinction (FE), the process by which learned fear responses are inhibited in safe contexts. This dysfunction contributes to maladaptive fear expression and is linked to altered neurocircuitry, particularly in the infralimbic cortex (IL), a key region in FE. Despite extensive evidence of impaired FE in patients with mild TBI and animal models, the specific mechanisms underlying this deficit remain poorly understood. This study aimed to address this gap by combining cued-FE behavior, local field potential recordings, and whole-cell patch-clamp techniques to investigate how mild TBI affects IL network activity and excitability in a mouse model of TBI. Our results demonstrate that mild lateral fluid percussion injury significantly impairs FE memory, as evidenced by an elevated cued-fear response during extinction testing 10 days post-injury. Field potential recordings revealed decreased activation of the IL network in both layers II/III and V, which was consistent with the observed behavioral deficits. Further analysis of synaptic physiology revealed an imbalance in excitatory and inhibitory neurotransmission (E/I imbalance) in the IL, characterized by reduced excitatory input and enhanced inhibitory input to neurons in both layers. Moreover, intrinsic excitability was altered in IL neurons after mild TBI. This study provides novel insights into how mild TBI disrupts the neurocircuitry underlying FE, specifically by suppressing IL excitability. These results highlight the importance of understanding the mechanistic disruptions in IL activity for developing therapeutic strategies to address fear-based disorders in patients with mild TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120033","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":"A Nomogram Predicts the Risk Factors for Post-Traumatic Cerebral Infarction in Polytrauma Patients with Traumatic Brain Injury.","authors":"Jianye Miao, Xin Qian, Zhenjun Miao, Jiayi Li, Litao Zhang, Renguang Zhang, Xianjun Ma, Yousef Rastegar-Kashkooli, Lang Liu, Nan Li, Qian Bai, Jiewen Zhang, Chao Jiang, Simeng Gu, Jian Wang, Junmin Wang","doi":"10.1089/neu.2024.0511","DOIUrl":"https://doi.org/10.1089/neu.2024.0511","url":null,"abstract":"<p><p>Post-traumatic cerebral infarction (PTCI) is a significant complication in polytrauma patients with traumatic brain injury (TBI). Identifying high-risk patients for early intervention is crucial. This study aims to investigate the independent risk factors for PTCI in polytrauma patients with TBI to establish and validate a prediction model. A retrospective analysis was conducted on 511 patients with TBI and multiple injuries admitted between January 2016 and July 2023. The patients were divided into groups based on whether they developed PTCI. Independent risk factors for PTCI were identified using univariable, Lasso, and multivariable logistic regression analysis. A nomogram was established to predict the risk factors for PTCI. The receiver operating characteristic (ROC) area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to determine the predictive accuracy, discrimination, and clinical effectiveness of the nomogram, respectively. In addition, the Hosmer-Lemeshow test was used to assess the goodness-of-fit. Clinically significant associations were observed between PTCI and factors such as cerebral hernia, traumatic subarachnoid hemorrhage, basilar skull fracture, shock index, platelets, platelet-lymphocyte ratio (PLR), prothrombin time, international normalized ratio, D-dimer, albumin, injury severity score, and Glasgow coma score (all <i>p</i> < 0.05). These variables screened by Lasso regression were incorporated in multivariate logistic regression. They identified cerebral hernia, basilar skull fracture, PLR, D-dimer, and albumin as independent risk factors for PTCI (all <i>p</i> < 0.05). The analysis results were visually represented using a nomogram. The AUC of the prediction cohort was 0.9 [95% confidence interval (95% confidence intercal (CI)): 0.84, 0.97], and of the validation cohort was 0.87 (95% CI: 0.79, 0.96). The nomogram prediction model demonstrates excellent performance according to the ROC, calibration curve, and DCA, providing valuable insights for the early identification of high-risk PTCI patients.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110942","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":"Volume Loss in the Mammillary Bodies, Fornix, and Other Papez Circuit Structures in Fighters with Traumatic Encephalopathy Syndrome.","authors":"Christopher Karakasis, Charles Bernick, Jennifer Bullen, Ken Sakaie, Stephen E Jones, Jonathan Lee","doi":"10.1089/neu.2025.0011","DOIUrl":"https://doi.org/10.1089/neu.2025.0011","url":null,"abstract":"<p><p>Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that can only be diagnosed on autopsy. Traumatic encephalopathy syndrome (TES) is a proposed diagnostic framework for the clinical syndrome of CTE that is based on patient history and clinical examination. Given that mammillary body and fornix volume loss has been demonstrated in CTE and is measurable on MRI, this study aims to investigate the relationship between TES status and <i>in vivo</i> mammillary body and fornix volumes to support the role of these structures as imaging biomarkers for TES. Additionally, associations with other structures of the Papez circuit and relevant cognitive tests were explored. This observational cohort study used data from a subset of fighters and control participants in the Professional Athletes Brain Health Study (PABHS). The relationship was examined between clinical groups (controls, TES-negative fighters, and TES-positive fighters) and automated measurements of mammillary body and fornix size. Manual measurements were also performed to confirm the automated results and demonstrate clinical relevance. Associations were assessed between mammillary body/fornix size, cognitive scores, and volumes of other structures including components of the Papez circuit. The sample consisted of 177 individuals (61 controls, 46 TES-positive fighters, and 70 TES-negative fighters). Automated measurements of mammillary body volumes were on average ∼7.6 mm³ (15%) smaller in TES-positive fighters than in TES-negative fighters and controls (<i>p</i> < 0.001 for both). Automated measurements of fornix volumes were on average 110.5 mm³ (24%) smaller in TES-positive fighters than in TES-negative fighters and 156.5 mm³ (29%) smaller in TES-positive fighters than in controls (<i>p</i> < 0.001 for both). Similar findings were observed with manual measurements. Decreased mammillary body and fornix size were associated with lower volumes in the other components of the Papez circuit/associated structures (<i>p</i> < 0.01 for all) and worse psychomotor (<i>p</i> = 0.001 for both) and memory (<i>p</i> < 0.001 for both) scores. This decrease in mammillary body and fornix size among TES-positive fighters suggests that increased exposure to repetitive head impacts damages these structures, and that imaging assessment of the mammillary bodies and fornix is a feasible biomarker to support the diagnosis of TES.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlating Magnetoencephalography, Diffusion Kurtosis Imaging, Biomechanics, and Neuropsychology in American Youth Football.","authors":"Natalie M Bell, Fang F Yu, Yin Xi, Amy L Proskovec, James M Holcomb, Sahil Chilukuri, Jillian E Urban, Christopher Vaughan, Jesse C DeSimone, Ben Wagner, Mark A Espeland, Alexander K Powers, Christopher T Whitlow, Joel D Stitzel, Joseph A Maldjian, Elizabeth M Davenport","doi":"10.1089/neu.2024.0222","DOIUrl":"https://doi.org/10.1089/neu.2024.0222","url":null,"abstract":"<p><p>This study investigated the association between repetitive head impacts (RHIs) and multimodal neuroimaging, biomechanical, and neuropsychological data in 72 youth football players and 17 controls, aged 8-12 years. Helmet sensors measured RHI exposure while imaging and psychological data were collected before and after the season. Risk-weighted exposure metrics were calculated to quantify cumulative RHI exposure. Changes in magnetoencephalography (MEG) and diffusion kurtosis imaging were analyzed by calculating voxel-wise difference, and z-score maps were thresholded with respect to controls. Using linear regression, statistically significant positive associations were observed between abnormally increased MEG-measured theta (5-7 Hz) power and RHI measures. No associations were found between RHI and other neuroimaging metrics. Football players and controls exhibited significant yet divergent associations between alpha (8-12 Hz) power as well as mean kurtosis and neuropsychological changes. These findings indicate a potential association between youth football players' exposure to RHI and neurophysiological alterations.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Topological Structure and Modular Interactions in Pediatric Patients with Complete Spinal Cord Injury: A Functional Brain Network Study.","authors":"Yu Wang, Ling Wang, Beining Yang, Haotian Xin, Qunya Qi, Yulong Jia, Xianglin Guo, Weimin Zheng, Xin Chen, Fang Li, Chuchu Sun, Qian Chen, Jubao Du, Jie Lu, Nan Chen","doi":"10.1089/neu.2024.0560","DOIUrl":"https://doi.org/10.1089/neu.2024.0560","url":null,"abstract":"<p><p>Traumatic complete spinal cord injury (CSCI) leads to severe impairment of sensory-motor function, and patients often suffer from neuropsychological deficits such as anxiety, depression, and cognitive deficits, which involve different brain functional modules. However, the alterations in modular organization and the interactions between these modules in pediatric patients with CSCI remain unclear. In this study, a total of 70 participants, including 34 pediatric CSCI patients and 36 healthy controls (HCs) aged 6 to 12 years, underwent whole-brain resting-state functional MRI. The functional networks were analyzed via a graph theory approach based on the 90-region Automated Anatomical Labeling (AAL 90) atlas, generating a 90 × 90 correlation matrix. Metrics for nodal, global, and modular scales were calculated to evaluate alterations in the network's topology. Between-group comparisons and partial correlation analysis were performed. Compared to HCs, pediatric CSCI patients exhibited significant decreases in nodal metrics, particularly in subcortical networks (SN) like the bilateral thalamus. Besides, the distribution of core nodes changed, with five newly added core nodes primarily located in the regions of the default mode network (DMN). For modular interactions, patients group presented increased connectivity within the DMN and between the DMN and the attention network (AN) but reduced connectivity between DMN and SN, DMN and vision network (VN), and AN and SN. Notably, the participation coefficient (Pc) of the TPOmid.L (left temporal pole: middle temporal gyrus) was positively correlated with motor scores, suggesting its potential as an indicator for evaluating the motor function in pediatric CSCI patients. Additionally, the patients demonstrated a different modular structure with significantly lower modularity. These findings suggest that functional network and modular alterations chiefly occur in emotional cognition and vision-associated regions, emphasizing the importance to focus on their psychocognitive well-being and providing evidence for visual-feedback related rehabilitation strategies.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023461","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":"Serum Biomarkers as Adjuncts to the National Institute for Health and Care Excellence Head Injury Guidelines (NG232, 2023) When Selecting Patients with Traumatic Brain Injury for Computed Tomography: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.","authors":"Daniel Whitehouse, Ana Mikolić, Endre Czeiter, Sophie Richter, Andras Buki, Kevin K Wang, Ewout Steyerberg, Andrew Maas, David Menon, Fiona Lecky, Virginia Newcombe","doi":"10.1089/neu.2024.0276","DOIUrl":"https://doi.org/10.1089/neu.2024.0276","url":null,"abstract":"<p><p>This article explores the diagnostic performance of a panel of six biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], neuron-specific enolase [NSE], S100 calcium-binding protein B [S100B], total tau [t-tau], and ubiquitin C-terminal hydrolase L1 [UCH-L1]) in the context of the \"2023 UK National Institute for Health and Care Excellence (NICE) Head Injury: Assessment and early management (NG232)\" guideline. Emphasis is placed on subjects where clinical equipoise remains concerning the decision for head computed tomography (CT), medium-risk subjects. All adult subjects from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset with a complete biomarker profile and interpretable CT scan within 24 h of injury were classified as high, medium, and low-risk according to the NICE NG232 Clinical Decision Rule (CDR) for CT head imaging following head injury. In subjects classified as medium-risk, the area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of biomarkers to identify those with (1) CT abnormality or (2) potential neurosurgical lesion, with CT considered the gold standard diagnosis. A time-to-biomarker sub-analysis was performed in subjects with a time from injury to sampling within 6 h, in keeping with current clinical usage of biomarkers. Among 1979 CENTER-TBI participants with sufficient clinical information to facilitate classification, 385 subjects were classified as medium-risk. Biomarker concentrations were significantly higher in those with traumatic CT abnormalities as compared with those without for all biomarkers aside from NSE (all <i>p</i> < 0.05). When sampled within 24 h of injury, GFAP demonstrated the best diagnostic performance for CT abnormality (AUC 0.81 [0.77-0.86]), with NFL, t-tau, and UCH-L1 showing moderate performance. At a threshold to provide a 95% sensitivity, GFAP, NFL, t-tau, and UCH-L1 demonstrated specificities ranging from 18% to 33% corresponding to a potential reduction of total CT images performed in these subjects by 14-23%. S100B and UCH-L1 showed improved performance when biomarker sampling time was limited to 6 h following injury. In intoxicated subjects with a persistent Glasgow Coma Score of 13-14, biomarker levels were significantly higher in subjects with CT abnormality as compared with those without. In conclusion, serum biomarkers demonstrate potential for the reduction in CT scan requirements in those classified as medium-risk in reference to the NG232 CDR criteria. These results highlight a need for further prospective studies on the use of diagnostic TBI biomarkers in current emergency medicine practice, with future consideration given to the integration of biomarkers in the NICE NG232 head injury guidelines.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-Reported Cognitive Difficulties and Their Modifiable Risk Factors in Former Elite Male Rugby League Players.","authors":"Katherine Grellman, Oliver J Smith, Douglas P Terry, Kenneth L Quarrie, Grant L Iverson, Andrew J Gardner","doi":"10.1089/neu.2024.0543","DOIUrl":"https://doi.org/10.1089/neu.2024.0543","url":null,"abstract":"<p><p>Participation in collision and contact sport in Australia-specifically rugby league-is popular. With recent attention to the possible long-term health consequences of head impact exposure during a contact or collision sport career, the importance of understanding the contribution of modifiable risk factors as they relate to cognitive function has been highlighted. Risk factors for cognitive decline in the general population include cardiovascular health, sleep disorders, chronic pain, depression, anxiety, smoking, physical impairment, and physical inactivity. This study examined the associations between these risk factors and self-reported cognitive function in 130 former elite male rugby league players in Australia. Respondents were recruited through a survey distributed through former player groups and via word of mouth. Self-reported cognitive function was assessed using the Quality of Life in Neurological Disorders-Applied Cognition General Concerns questionnaire. Risk factors for cognitive decline were self-reported, with questions collated from multiple validated sources, with each selected to explore specific categories of cognitive function. They included: questions from the Football Players Health Study at Harvard; The Australian Mental Health and Wellbeing Survey 2007; the Patient Reported Outcome Measurement Information System Item Banks for Pain Interference and Physical Function; and the Patient Health Questionnaire. Of the 130 participants, 43.1% (<i>n</i> = 56) reported perceived cognitive impairment. When adjusted for age and number of concussion-related signs and symptoms experienced during their career, predictors of perceived cognitive difficulties included less than 5 h of sleep on average, history of stroke, current clinical symptoms of anxiety, physical impairment, and number of risk factors. The number of concussion-related signs and symptoms experienced was not related to perceived cognitive impairment, although it was associated with specific risk factors. Early education and intervention by medical professionals to manage these risk factors may provide a pathway for improving perceived cognitive health and functioning in former elite male rugby league players in the future.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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":"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":"814-831"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","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}