Journal of neurotrauma最新文献

{"title":"Evaluating the Efficacy of Chronic Galantamine on Sustained Attention and Cholinergic Neurotransmission in A Pre-Clinical Model of Traumatic Brain Injury.","authors":"Eleni H Moschonas, Haley E Capeci, Ellen M Annas, Veronica B Domyslawski, Jade A Steber, Hailey M Donald, Nicholas R Genkinger, Piper L Rennerfeldt, Rachel A Bittner, Vincent J Vozzella, Jeffrey P Cheng, Anthony E Kline, Corina O Bondi","doi":"10.1089/neu.2024.0173","DOIUrl":"10.1089/neu.2024.0173","url":null,"abstract":"<p><p>Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by <i>in vivo</i> microdialysis. In Experiment 1, adult male rats (<i>n</i> = 10-15/group) trained in the 3-choice serial reaction time (3-CSRT) test were randomly assigned to controlled cortical impact (CCI) or sham surgery and administered GAL (0.5, 2.0, or 5.0 mg/kg; i.p.) or saline vehicle (VEH; 1 mL/kg; i.p) beginning 24-h post-surgery and once daily thereafter for 27 days. Measures of sustained attention and distractibility were assessed on post-operative days 21-25 in the 3-CSRT, following which cortical lesion volume and basal forebrain cholinergic cells were quantified on day 27. In Experiment 2, adult male rats (<i>n</i> = 3-4/group) received a CCI and 24 h later administered (i.p.) one of the three doses of GAL or VEH for 21 days to quantify the dose-dependent effect of GAL on <i>in vivo</i> ACh efflux in the mPFC. Two weeks after the CCI, a guide cannula was implanted in the right mPFC. On post-surgery day 21, baseline and post-injection dialysate samples were collected in a temporally matched manner with the cohort undergoing behavior. ACh levels were analyzed using reverse phase high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. Cortical lesion volume was quantified on day 22. The data were subjected to ANOVA, with repeated measures where appropriate, followed by Newman-Keuls <i>post hoc</i> analyses. All TBI groups displayed impaired sustained attention versus the pooled SHAM controls (<i>p</i>'s < 0.05). Moreover, the highest dose of GAL (5.0 mg/kg) exacerbated attentional deficits relative to VEH and the two lower doses of GAL (<i>p</i>'s < 0.05). TBI significantly reduced cholinergic cells in the right basal forebrain, regardless of treatment condition, versus SHAM (<i>p</i> < 0.05). <i>In vivo</i> microdialysis revealed no differences in basal ACh in the mPFC; however, GAL (5.0 mg/kg) significantly increased ACh efflux 30 min following injection compared to the VEH and the other GAL (0.5 and 2.0 mg/kg) treated groups (<i>p</i>'s < 0.05). In both experiments, there were no differences in cortical lesion volume across treatment groups (<i>p</i>'s > 0.05). In summary, albeit the higher dose of GAL increased ACh release, it did not improve measures of sustained attention or histopathological markers, thereby partially supporting the hypothesis and providing the impetus for further investigations into alternative cholinergic pharmacotherapies such as nAChR positive a","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2428-2441"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590538","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":"Bradykinin 2 Receptors Mediate Long-Term Neurocognitive Deficits After Experimental Traumatic Brain Injury.","authors":"Antonia Clarissa Wehn, Igor Khalin, Senbin Hu, Biyan Nathanael Harapan, Xiang Mao, Shiqi Cheng, Nikolaus Plesnila, Nicole A Terpolilli","doi":"10.1089/neu.2024.0042","DOIUrl":"10.1089/neu.2024.0042","url":null,"abstract":"<p><p>The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. B2R KO mice (heterozygous, homozygous) and wild-type (WT) littermates (<i>n</i> = 10/group) were subjected to controlled cortical impact (CCI) TBI. Lesion size was evaluated by magnetic resonance imaging up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological Severity Score, Beam Walk, and Barnes maze test. Ninety days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R-deficient and WT animals 3 months after injury; however, hippocampal damage was reduced in B2R KO mice (<i>p</i> = 0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function 3 months after TBI (<i>p</i> = 0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex (<i>p</i> = 0.0003) and hippocampus (<i>p</i> < 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2442-2454"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179911","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":"Trajectories of Recovery Following Traumatic Brain Injury Among Older Medicare Beneficiaries.","authors":"Jennifer S Albrecht, Chixiang Chen, Jason R Falvey","doi":"10.1089/neu.2023.0502","DOIUrl":"10.1089/neu.2023.0502","url":null,"abstract":"<p><p>It is well-known that older adults have poorer recovery following traumatic brain injury (TBI) relative to younger adults with similar injury severity. However, most older adults do recover well from TBI. Identifying those at increased risk of poor recovery could inform appropriate management pathways, facilitate discussions about palliative care or unmet needs, and permit targeted intervention to optimize quality of life or recovery. We sought to explore heterogeneity in recovery from TBI among older adults as measured by home time per month, a patient-centered metric defined as time spent at home and not in a hospital, urgent care, or other facility. Using data obtained from Medicare administrative claims data for years 2010-2018, group-based trajectory modeling was employed to identify unique trajectories of recovery among a sample of United States adults age 65 and older who were hospitalized with TBI. We next determined which patient-level characteristics discriminated poor from favorable recovery using logistic regression. Among 20,350 beneficiaries, four unique trajectories were identified: poor recovery (<i>n</i> = 1929; 9.5%), improving recovery (<i>n</i> = 2,793; 13.7%), good recovery (<i>n</i> = 13,512; 66.4%), and declining recovery (<i>n</i> = 2116; 10.4%). The strongest predictors of membership in the poor relative to the good recovery trajectory group were diagnosis of Alzheimer's disease and related dementias (ADRD; odd ratio [OR] 2.42; 95% confidence interval [CI] 2.16, 2.72) and dual eligibility for Medicaid, a proxy for economic vulnerability (OR 5.13; 95% CI 4.59, 5.74). TBI severity was not associated with recovery trajectories. In conclusion, this study identified four unique trajectories of recovery over one year following TBI among older adults. Two-thirds of older adults hospitalized with TBI returned to the community and stayed there. Recovery of monthly home time was complete for most by 3 months post injury. An important sub-group comprising 10% of patients who did not return home was characterized primarily by eligibility for Medicaid and diagnosis of ADRD. Future studies should seek to further characterize and investigate identified recovery groups to inform management and development of interventions to improve recovery.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2377-2384"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570724","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 after Traumatic Brain Injury with and Without Computed Tomography.","authors":"Ana Mikolić, Shuyuan Shi, William Panenka, Jeffrey R Brubacher, Frank X Scheuermeyer, Lindsay D Nelson, Noah D Silverberg","doi":"10.1089/neu.2024.0332","DOIUrl":"https://doi.org/10.1089/neu.2024.0332","url":null,"abstract":"<p><p>Our recent improved understanding of traumatic brain injury (TBI) comes largely from cohort studies of TBI patients with indication for computed tomography (CT). Using CT head as an inclusion criterion may overestimate poor outcomes after TBI with Glasgow Coma Scale (GCS) 13-15. We aimed to compare outcomes after TBI in adults who had a head CT scan (with negative findings) versus those who had no CT when presenting to an emergency department. This was a secondary analysis of a trial that recruited adults with GCS = 13-15 after TBI in Vancouver, Canada. We included 493 participants (18-69 years, 54% female), after removing <i>n</i> = 19 with traumatic abnormalities on CT (intracranial and/or skull fracture). Outcomes were Glasgow Outcome Scale Extended (GOSE), Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Patient Health Questionnaire (PHQ)-9, and generalized anxiety disorder (GAD)-7 at 6 months post-injury. Over half (55%) of participants received a CT. At 6 months, 55% of participants with CT and 49% without CT had functional limitations on GOSE; 32% with CT and 33% without CT reported severe post-concussion symptoms (RPQ ≥16); 26% (with CT) and 28% (without CT) screened positive for depression (PHQ-9 ≥ 10), and 25% (with CT) and 28% (without CT) screened positive for anxiety (GAD-7 ≥ 8). In regression adjusted for personal variables, participants with CT had somewhat higher odds of worse functioning (ordinal GOSE; 1.4, 95% CI 1.0-2.0) but similar odds of severe post-concussion symptoms (1.1, 95% CI: 0.7-1.7), and depression (1.1, 95% CI: 0.7-1.7) and anxiety (1.0, 95% CI: 0.6-1.5) symptoms. Adults with and without head CT have mostly comparable outcomes from TBI with GCS = 13-15. Requiring CT by clinical indication for study entry may not create problematic selection bias for outcome research.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522139","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":"Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury is Linked to Microstructural Plasticity in Prefrontal White Matter.","authors":"Haleh Karbasforoushan, Jamie Wren-Jarvis, Anna Hwang, Rachel Santiago, Sky Raptentsetsang, Lanya T Cai, Jaclyn Xiao, Brian A Maruyama, Gary M Abrams, Tatjana Novakovic-Agopian, Pratik Mukherjee","doi":"10.1089/neu.2023.0229","DOIUrl":"10.1089/neu.2023.0229","url":null,"abstract":"<p><p>Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522138","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 Combination of Low Doses of Lithium and Valproate Improves Cognitive Outcomes after Mild Traumatic Brain Injury.","authors":"John B Redell, Mark E Maynard, Michael J Hylin, Kimberly N Hood, Andrea Sedlock, Dragan Maric, Jing Zhao, Anthony N Moore, Badrinath Roysam, Shibani Pati, Pramod K Dash","doi":"10.1089/neu.2024.0311","DOIUrl":"https://doi.org/10.1089/neu.2024.0311","url":null,"abstract":"<p><p>The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + VPA) for 3 weeks after a moderate-to-severe controlled cortical impact injury reduced cortical tissue loss and improved motor function. Since both lithium and valproate can exhibit toxicity at high doses, it would be beneficial to determine if this combination treatment is effective when administered at low doses and for a shorter duration, and if it can improve cognitive function, after a mild diffuse TBI. In the present study, we tested if the combination of low doses of lithium (1 mEq/kg or 0.5 mEq/kg) plus valproate (20 mg/kg) administered for 3 days after a mild fluid percussion injury can improve hippocampal-dependent learning and memory. Our data show that the combination of low-dose Li + VPA improved spatial learning and memory, effects not seen when either drug was administered alone. In addition, postinjury Li + VPA treatment improved recognition memory and sociability and reduced fear generalization. Postinjury Li + VPA also reduced the number of anti-ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia counted using a convolutional neural network, indicating a reduction in neuroinflammation. These findings indicate that low-dose Li + VPA administered acutely after mTBI may have translational utility to reduce pathology and improve cognitive function.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502332","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":"Magnetic Resonance Imaging Parameters in the Subacute Phase after Traumatic Cervical Spinal Cord Injury: A Prospective, Observational Longitudinal Study. Part 1: Conventional Imaging Characteristics.","authors":"Lukas Grassner, Iris Leister, Florian Högel, Ludwig Sanktjohanser, Matthias Vogel, Orpheus Mach, Doris Maier, Andreas Grillhösl","doi":"10.1089/neu.2023.0592","DOIUrl":"https://doi.org/10.1089/neu.2023.0592","url":null,"abstract":"<p><p>Magnetic resonance imaging (MRI) remains the gold standard for evaluating spinal cord tissue damage after spinal cord injury (SCI). Several MRI findings may have some prognostic potential, but their evolution over time, especially from the subacute to the chronic phase has not been studied extensively. We performed a prospective observational longitudinal study exploring the evolution of MRI parameters from the subacute to chronic phase after human traumatic cervical SCI. The study, conducted between 2016 and 2021, involved standardized neurological examinations and MRI scans 1 month, 3 months, and 1 year after SCI<i>.</i> The study cohort comprises 52 patients with cervical SCI. Patients were classified into AIS grades (American Spinal Injury Association Impairment Scale), and neurological recovery was assessed using the Integrated Neurological Change Score. The MRI protocol included various routine sequences, allowing the evaluation of established parameters such as intramedullary hemorrhage, lesion dimensions, maximum spinal cord compression, and various grading scales. The persistence of intramedullary hemorrhage one month after injury was associated with worse lower extremity motor scores and pinprick values after 3 months, and also in the chronic phase. In addition, dorsal column T2-weighted hyperintensities detected 3 months post-injury and in the chronic phase were related to lower pinprick sensory scores. The basic score and Sagittal Grade at 1 month were predictive for motor function 3 months after SCI and for neurological recovery between 1 and 3 months after injury. The study contributes valuable insights into the utility of routine MRI sequences for evaluating traumatic cervical SCI during the subacute to chronic phase. The identified MRI parameters and scores offer prognostic information and could support clinical decision-making.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502334","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":"Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.","authors":"Gregory J R States, Trevor Clark, Darlene A Burke, Alice Shum-Siu, David S K Magnuson","doi":"10.1089/neu.2023.0640","DOIUrl":"https://doi.org/10.1089/neu.2023.0640","url":null,"abstract":"<p><p>Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502335","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":"Cell-Specific Gene Expressions Underlie Selective White Matter Loss Vulnerability in Mild Traumatic Brain Injury.","authors":"Xiaoyan Jia, Wenpu Zhao, Haonan Zhang, Xiang Zhang, Qiuyu Ji, Xuan Li, Yizhen Pan, Xiaofan Jiang, Jie Zhang, Lijun Bai","doi":"10.1089/neu.2024.0022","DOIUrl":"https://doi.org/10.1089/neu.2024.0022","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), a risk factor for later-life dementia, leads to salient brain atrophy, particularly in the white matter. It is not clear how white matter atrophy progresses or why some brain regions are damaged while others are spared. We hypothesized that spatial variations of cell-specific gene expression contributed to the selective white matter loss vulnerability following mild TBI (mTBI). Gene expression data were sourced from the publicly available Allen Human Brain Atlas, which comprises microarray data spanning nearly the entire brain, derived from six neurologically normal adult donors. A total of 100 patients with acute stage (within 7 days post-injury) mTBI were enrolled. Of these, 60 patients were followed up at 3 months post-injury and 37 were followed up at 6-12 months post-injury. In addition, 59 healthy controls (HCs), matched for age, gender, and education, were included for comparative analysis. White matter volume changes were analyzed at both the acute stage, 3 months, and 6-12 months follow-up in mTBI patients compared with HCs. Patients with mTBI exhibited significant white matter atrophy in the frontal, parietal, and temporal cortices at 3 months post-injury, which even persisted at 6-12 months follow-up. In addition, mTBI patients with cognitive deficits showed more severe brain atrophy compared with those without cognitive deficits. Crucially, the gene expression marking endothelial cells and S1 pyramidal neurons were associated with increased brain atrophy, whereas the gene expression marking microglia and CA1 pyramidal neurons were associated with decreased brain atrophy in mTBI patients at 3 months post-injury. Microglia and endothelial cells can explain 23.6% of regional variations in the white matter atrophy. These findings suggested that modulating cellular activation, especially by promoting microglial activation at 3 months post-injury, might be a promising approach to prevent white matter atrophy, enhance cognitive outcomes, and reduce the risk of later-life dementia.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502333","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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}