Neurotrauma reports最新文献

{"title":"High-Frequency Analysis of the Cerebral Physiological Impact of Ketamine in Acute Traumatic Neural Injury.","authors":"Davis McClarty, Logan Froese, Tobias Bergmann, Kevin Y Stein, Amanjyot S Sainbhi, Abrar Islam, Nuray Vakitbilir, Noah Silvaggio, Izabella Marquez, Alwyn Gomez, Frederick A Zeiler","doi":"10.1089/neur.2024.0146","DOIUrl":"10.1089/neur.2024.0146","url":null,"abstract":"<p><p>Acute traumatic neural injury, also known as traumatic brain injury (TBI), is a leading cause of death. TBI treatment focuses on the use of sedatives, vasopressors, and invasive intracranial pressure (ICP) monitoring to mitigate ICP elevations and maintain cerebral perfusion pressure (CPP). While common sedatives such as propofol and fentanyl have significant side effects, ketamine is an attractive alternative due to its rapid onset and cardiovascular stability. Despite these benefits, ketamine's use remains controversial due to historical concerns about increasing ICP. Using high-frequency monitoring, this retrospective study compared cerebral pressure-flow dynamics in patients with moderate/severe TBI who received ketamine with those who did not. Statistical analysis included descriptive statistics, comparisons within and between patients receiving ketamine, and evaluation of physiological response around incremental dose changes in ketamine. Various cerebral physiological indices were analyzed, including ICP, CPP, regional cerebral oxygen delivery, intracranial compliance, and cardiovascular reactivity metrics. A total of 122 patients were studied, with 17 receiving ketamine (median age: 37 years) and 105 not receiving ketamine (median age: 42 years). Results indicated higher median ICP in the ketamine group compared with the no ketamine group (9.05 mmHg and 14.00 mmHg, respectively, <i>p</i> = 0.00017); however, this is likely due to differences in patient characteristics and injury severity between the groups. No significant differences were observed in any other index of cerebral pressure-flow dynamics or between any incremental dose change condition. These findings suggest that ketamine does not significantly impact cerebral pressure-flow dynamics, challenging historical concerns about its use in patients with TBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"232-241"},"PeriodicalIF":1.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Prognostication in Pediatric Severe Traumatic Brain Injury in South America: Development of a Local Pediatric-Specific Model and Validation of Established Models.","authors":"Madeline E Greil, Omar Abdelmaksoud, Lauren L Agoubi, Julia Velonjara, Jin Wang, Gustavo Petroni, Silvia Lujan, Nahuel Guadagnoli, Michael J Bell, Monica S Vavilala, Robert H Bonow","doi":"10.1089/neur.2024.0157","DOIUrl":"10.1089/neur.2024.0157","url":null,"abstract":"<p><p>Prognostication in severe traumatic brain injury (sTBI) is important, but few models are pediatric-specific and from low- and middle-income countries where head computed tomography (CT) scans may not be routinely available. We assessed intensive care unit admission risk factors for early mortality and unfavorable outcome in a secondary analysis of 115 children (mean 7.0 years, standard deviation [sd] 5.3) receiving sTBI (Glasgow Coma Scale [GCS] total score ≤8 or GCS motor ≤5) care in South America who participated in the 16 hospital Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina trial between September 1, 2019, and July 13, 2020. Outcomes were 14-day mortality and 3-month Glasgow Outcome Scale-Extended for Pediatrics (GOS-E Peds). First, we examined univariate associations of predictors with the two outcomes. Then, two PEGASUS logistic regression models (core model with only clinical variables and full model with both clinical and CT variables) for each of the outcomes were derived. Models were examined for fit and compared for prediction. The locally derived PEGASUS model shows a good core prediction of 14-day (area under the receiver operating characteristic curve [AUROC]: 0.92; confidence interval [CI]: 0.85-0.99) and 3-month (AUROC 0.82 CI 0.73-0.91) outcomes; findings are similar to the International Mission on Prognosis and Analysis of Randomized Controlled Trials in TBI (IMPACT), Corticosteroid Randomization after Significant Head Injury (CRASH), and Petroni models. There was no difference between core and full models in prognosticating 14-day mortality, but IMPACT (<i>p</i> = 0.01) and PEGASUS (<i>p</i> = 0.01) full models outperformed their respective core models for 3-month GOS-E Peds. Core models, including PEGASUS, can be used but full models are preferred to prognosticate outcomes after pediatric sTBI in South America. PEGASUS model validation against external datasets is needed.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"171-182"},"PeriodicalIF":1.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinically Relevant Mouse Model of Concussion Incorporating High Rotational Forces.","authors":"Elizabeth M Teasell, Emilie Potts, Nicole Geremia, Lihong Lu, Xiaoyun Xu, Haojie Mao, Arthur Brown","doi":"10.1089/neur.2024.0165","DOIUrl":"10.1089/neur.2024.0165","url":null,"abstract":"<p><p>Clinically relevant models of concussion are critical in understanding the pathophysiology of concussion and its long-term outcomes. To bridge the gap between preclinical and clinical research, animal models of concussion should be produced by mild traumatic brain injuries (mTBIs) that possess the same physical and biomechanical properties found in the mTBIs that cause concussion in humans. Specifically, to have good construct validity the mTBIs used in animal models of concussion should feature closed-head impacts with unrestrained head and body motion, resulting in peak angular velocities that approximate the human experience. We describe a mouse model of concussion using a cortical impactor to deliver closed-head mTBIs. Mice are placed on a break-away platform that allows free head and body movement during and after impact resulting in rapid head rotation. We assessed this model of concussion in over 100 mice carrying humanized versions of the genes encoding the amyloid precursor protein and tau. We found that this method consistently produced injuries with peak angular velocities in mice that, when scaled, approximated the average peak angular velocities reported in concussive football impacts. Face validity of this model of concussion was evaluated by histopathology and revealed that three impacts delivered 24 hours apart led to diffuse axonal injury, astrogliosis, and microglial activation one week after injury, particularly in white matter tracts aligned orthogonally to the axis of rotation. Persistent axonal degeneration was observed up to 6 months postinjury. This mouse model of concussion captures key biomechanical and pathological features of human concussions.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"184-190"},"PeriodicalIF":1.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Small-Molecule TrkB/TrkC Ligand Promotes Neurogenesis and Behavioral Recovery Following Traumatic Brain Injury.","authors":"Jian Shi, Tao Yang, Yibing Li, Lily Zhong, Frank M Longo, Stephen M Massa","doi":"10.1089/neur.2024.0117","DOIUrl":"10.1089/neur.2024.0117","url":null,"abstract":"<p><p>Tropomyosin receptor-kinase B (TrkB) and TrkC neurotrophin receptors promote neuronal growth and differentiation during the development and maintenance of structural integrity and plasticity in adult animals. Here, we test the hypotheses that activation of TrkB and TrkC will mitigate neuronal damage and loss, and behavioral deficits induced by traumatic brain injury (TBI). LM22B-10 (C10), a blood-brain barrier permeant small-molecule TrkB/TrkC co-activator, significantly increased proliferation, survival, and enhanced differentiation of neuronal progenitor cells <i>in vitro</i>. Following controlled cortical impact injury in rats, LM22B-10 administration increased the proliferation of doublecortin-expressing (DCX) cells in the hippocampus and significantly reduced cell death in the injured cortex. Interestingly, in studies of behavior, LM22B-10 promoted anxiety-like behavior and diminished spatial memory performance in the Barnes maze in sham-TBI animals but improved both of these behaviors in injured rats, a bimodal response suggesting the possibility that excess neurotrophic activity may be detrimental in uninjured animals but compensatory after injury. Thus, TrkB/TrkC agents may constitute a new therapeutic avenue for TBI but will require further study to determine safe and effective applications.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"195-209"},"PeriodicalIF":1.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Plasma Complement C1Q Measured Subacutely after Traumatic Brain Injury Is Associated with Poor Functional Outcome Independent of Initial Injury Severity.","authors":"Tracy Butler, Kewei Chen, Abigail Patchell, Xiangling Mao, Dikoma Shungu, Diany Paola Calderon, Jeanne T Paz, Sudhin A Shah","doi":"10.1089/neur.2024.0152","DOIUrl":"10.1089/neur.2024.0152","url":null,"abstract":"<p><p>Following traumatic brain injury (TBI), secondary processes, including inflammation, contribute significantly to long-term cognitive and functional impairments. Targeting these secondary processes during the subacute period after TBI represents a feasible therapeutic target. This study investigates the role of complement factor 1q (C1Q) in TBI recovery. Motivated by our rodent studies showing that thalamic inflammation post-TBI is dependent on C1Q and that blocking C1Q during the subacute period can prevent thalamic inflammation and improve aspects of TBI outcome, particularly sleep, we measured plasma C1Q levels 3-6 months post-injury in 27 patients with TBI ranging from complicated mild to severe, as well as 30 controls. TBI patients had significantly higher plasma C1Q levels (<i>p</i> = 0.031). We assessed the correlation between plasma C1Q and functional outcomes using the Glasgow Outcome Scale-Extended (GOSE), controlling for initial injury severity. Higher plasma C1Q levels were associated with worse functional outcomes (rho = -0.395, <i>p</i> = 0.046), independent of initial injury severity. These findings suggest that subacute plasma C1Q may be a novel prognostic biomarker for TBI outcomes. More importantly, subacute plasma C1Q may provide a window into ongoing, C1Q-mediated maladaptive neuroinflammatory processes after TBI that we have shown to be remediable in rodents using a safe-in-human drug that blocks C1Q. Since the initial injury cannot be changed, the ability to intervene subacutely could provide critical therapeutic benefits to the millions affected by TBI each year.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"190-194"},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Spinal Cord Swelling in Acute Traumatic Spinal Cord Injury.","authors":"Hasan Asif, Ravindran Visagan, Ellaine Boseta, Argyro Zoumprouli, Marios C Papadopoulos, Samira Saadoun","doi":"10.1089/neur.2025.0005","DOIUrl":"10.1089/neur.2025.0005","url":null,"abstract":"<p><p>We hypothesized that the Monro-Kellie doctrine, a key principle in traumatic brain injury (TBI), also applies in traumatic spinal cord injury (TSCI). By analyzing 9986 h of intraspinal pressure (ISP) monitoring data from 79 TSCI patients, we show that concepts developed to quantify compensatory reserve in TBI may be analogously defined in TSCI, termed ISP pulse amplitude (sAMP), spinal compensatory reserve index (sRAP), and ISP waveform shape. As ISP increases beyond 15 mmHg, compensatory reserve becomes impaired (sAMP rises and sRAP becomes positive). As ISP increases beyond 20 mmHg, the morphology of the ISP waveform changes from three peaks (P1, P2, P3) with P1 dominant, to three peaks with P2 dominant, to a rounded signal. Key differences in TSCI, compared with TBI, are no plateau ISP waves, and no critical ISP beyond which sAMP decreases and sRAP becomes negative. Four factors were associated with increased spinal cord swelling or reduced spinal cord compliance: thoracic level of injury, no laminectomy, delayed surgery, and more severe injury. We also hypothesized that, as in TBI, the spinal cord maximally swells a few days after injury. Serial ultrasound scans of the injured spinal cords in 9 patients and plots of change from baseline in ISP, sAMP, and sRAP versus time in 79 patients revealed delayed maximal cord swelling within 5 days of surgery. We conclude that the spinal Monro-Kellie concept allows the spinal compensatory reserve to be quantified. Our data show that spinal compensatory reserve becomes exhausted as ISP increases above 15-20 mmHg and that there is delayed cord swelling after injury, which implies that adequate cord decompression confirmed during surgery by ultrasound may not persist postoperatively.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"158-170"},"PeriodicalIF":1.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catastrophizing Thoughts and Fear-Avoidance Behavior Are Related to Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury.","authors":"Lynn Hecker, Skye King, Melloney Wijenberg, Chantal Geusgens, Sven Stapert, Jeanine Verbunt, Caroline Van Heugten","doi":"10.1089/neur.2024.0136","DOIUrl":"10.1089/neur.2024.0136","url":null,"abstract":"<p><p>A small percentage of patients with mild traumatic brain injury (mTBI) does not follow the expected recovery trajectory but develop persistent post-concussion symptoms (PCS). The fear-avoidance model (FAM) is a general biopsychosocial model that may potentially explain the development and continuation of persistent PCS for a subgroup of patients. The aim of the present study was to investigate if the FAM can (at least partially) explain PCS at 3 and 6 months post-mTBI by investigating associations between the elements of the FAM. A prospective, longitudinal, multicenter cohort study with outcome assessments at 2 weeks, 3 months, and 6 months post-mTBI was conducted in 163 patients with mTBI recruited from the emergency department and neurology department within 2 weeks post-mTBI. The FAM components PCS, catastrophizing, fear-avoidance behavior and depressive symptoms correlated significantly with each other at 3 months post-mTBI (<i>p</i> < 0.01) and correlations ranged from 0.40 to 0.72. No significant correlations were found between disuse and the other components. Depressive symptoms at 3 months post-mTBI significantly correlated with PCS at 6 months post-mTBI. Our results suggest that the FAM could be an explanatory model for the development of persistent PCS. This implies that treatment development for patients with persistent PCS could be aimed at the components of the FAM, such as exposure therapy to reduce catastrophizing and avoidance behavior.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"148-157"},"PeriodicalIF":1.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health and Lifetime History of Parent-Reported Concussion in School-Aged Children and Adolescents in the United States.","authors":"Grant L Iverson, Julia E Maietta, Altaf Saadi, Nathan E Cook","doi":"10.1089/neur.2024.0083","DOIUrl":"10.1089/neur.2024.0083","url":null,"abstract":"<p><p>Social determinants of health (SDoH) are environmental and socioeconomic factors that indirectly or directly influence health. This study examined whether SDoH that might relate to health literacy or access to health care are associated with lifetime history of parent-reported concussion in school-aged children and adolescents in the United States. We hypothesized that lower parental education, living in poverty, and speaking a language other than English as the primary language in the home would be associated with a lower lifetime history of concussion. Participants were parents or caregivers of 34,077 children and adolescents (ages 5-17) from the 2021 National Survey of Children's Health. SDoH variables included primary language spoken at home, family income, parental level of education, and current health insurance. Univariable analyses assessed the individual association of each SDoH variable with lifetime history of concussion. A multivariable logistic regression was used to assess the combined association of SDoH variables and other demographic predictors with lifetime concussion history. In the univariable models, male gender, older age, sports participation, and having current health care coverage were associated with a higher lifetime history of concussion. Hispanic/Latino ethnicity, primary language spoken at home other than English, lower level of parental education, living in poverty, and Black or Asian race were associated with lower lifetime history of concussion. In a multivariable model, significant independent predictors of lower lifetime concussion history were lower level of parental education, not speaking English as the primary language at home, and identifying as Black or Asian. It is possible that lower parental education, living in poverty, and speaking a language other than English as the primary language spoken are factors relating to lower concussion-related health literacy. Lower health literacy might contribute to families being less likely to (i) recognize the symptoms of concussion and (ii) seek medical evaluation for the injury.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"20-31"},"PeriodicalIF":1.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Magnetic Resonance Imaging Brain Age Investigation in Athletes with Persistent Postconcussion Syndrome.","authors":"Samuel Guay, Camille Charlebois-Plante, Sophie-Andrée Vinet, Marie-Eve Bourassa, Louis De Beaumont","doi":"10.1089/neur.2024.0094","DOIUrl":"10.1089/neur.2024.0094","url":null,"abstract":"<p><p>Brain age prediction algorithms using structural magnetic resonance imaging (MRI) estimate the biological age of the brain by comparing it to a normal aging trajectory, allowing for the identification of deviations that may indicate slower or accelerated biological aging. Traumatic brain injury (TBI) and sports-related concussion (SRC) have been associated with greater brain age gap (BAG) compared to healthy controls. In this study, we aimed to investigate BAG in athletes suffering from persistent postconcussion syndrome (PCS+) compared to PCS- athletes, and used SHapley Additive exPlanations (SHAP), an explainable artificial intelligence framework, to provide further details on which specific features drive the brain age predictions. Brain age was derived from T1-weighted MRI images in a cohort of 50 athletes (24 with PCS+) from 22 to 73 years old from the general population. The results revealed that athletes with PCS+ had a brain age approximately 5 years older than the PCS- athletes, with no clinical variable associated with it. Exploratory analyses also showed a greater brain age in athletes who self-reported five or more SRCs. Regarding SHAP, the third ventricle was found to be the most informative feature in the PCS+ group, while the superior temporal sulcus posterior area was more informative in the PCS- group. This study demonstrated the potential of using brain age and explainable artificial intelligence frameworks to study athletes with PCS. Further research is needed to explore the underlying mechanisms driving brain aging in this population and to identify potential biomarkers for early detection and intervention.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"136-147"},"PeriodicalIF":1.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-Infrared Imaging of Glymphatic Clearance in a Pre-Clinical Model of Repetitive Closed Head Traumatic Brain Injury.","authors":"Eleftheria Michalaki, Alexis N Pulliam, Pooja M Datta Roy, J Brandon Dixon, Michelle C LaPlaca","doi":"10.1089/neur.2024.0128","DOIUrl":"10.1089/neur.2024.0128","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a major health disorder for which there are few treatments. The glymphatic system is the brain's inbuilt lymphatic-like system that is thought to be responsible for clearing waste products from the brain to the lymph nodes. Although there is evidence that glymphatic drainage is crucial for brain homeostasis, its role in TBI pathogenesis remains elusive. Here, we investigated how glymphatic clearance is altered following TBI in rats using real-time non-invasive imaging. Twenty-four hours following repetitive closed-head TBI or sham conditions, we injected infrared dye intraventricularly and used near-infrared (NIR) imaging to quantify signal intensity, intensity over time, and appearance time of NIR dye in different brain regions. TBI yielded a lower NIR signal and lower rate of NIR dye change in the lateral ventricle and surrounding parietal cortex compared with sham conditions, indicating reduced cerebrospinal fluid perfusion. NIR dye appearance took significantly longer to reach the anterior regions of the brain, while perfusion to the posterior of the brain was faster in TBI compared with sham animals. Aquaporin-4 (AQP4) expression was reduced 24 h after TBI across all cortical regions examined in the posterior of the brain and in the ventral cortex at all coronal levels, suggesting a complex relationship between AQP4 and glymph function. Furthermore, NIR imaging revealed that NIR dye was detectable in the cervical lymph nodes (CLNs) of sham animals but not in TBI animals, yet there was evidence of blood accumulation in the CLNs of TBI animals, suggesting that TBI-related extravascular blood is removed through the glymph system. These data indicate that TBI disrupts normal brain efflux kinetics and reduces glymphatic drainage to the CLNs, demonstrating that restoring glymphatic function may be a promising therapeutic target.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"115-128"},"PeriodicalIF":1.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}