Neurotrauma reports最新文献

Intimate partner violence (IPV) frequently results in brain injury (IPV-BI) among survivors, with potential long-term effects for both physical and psychological health. This study aimed to examine the impact of chronic IPV-BI on postural control with (eyes open, [EO]) and without (eyes closed, [EC]) visual cues. We hypothesized that more exposure to a history of IPV-BI would be associated with greater postural control disruptions. During quiet stance, a force plate recorded forces and moments from which center of pressure (COP) variables were calculated to assess postural control. In addition, we sought to explore the relationship between psychological factors with assessments including indices of post-traumatic stress disorder (PTSD) (Clinician-Administered PTSD Scale), depression (Beck's Depression Inventory), and anxiety (Beck's Anxiety Inventory). Forty women survivors of IPV between the ages of 20 and 50 years participated, with the extent of exposure to IPV-BI measured using the Brain Injury Severity Assessment (BISA) tool on a scale of 0-8. Mediolateral (ML) COP displacement amplitude and variability, as well as anteroposterior (AP) COP velocity, was greater with EC than EO (p < 0.05). When participants were stratified into those with a low (0-2) and high (6-8) BISA score, participants in the high BISA (6-8) group exhibited greater COP area, ML COP amplitude and variability than those in the low BISA group (0-2; p < 0.05). Multiple linear regression analysis revealed that, independent of BISA score, PTSD symptoms contributed to changes in balance variables during the EO condition (p < 0.05). Taken together, our findings indicate the extent of exposure to a previous history of IPV-BI is linked to impairments in postural control as assessed by a variety of COP parameters. Given that standing balance is critical for function and mobility during activities of daily living, postural control assessments could serve as a valuable tool in diagnosing chronic IPV-BI. Thus, our study emphasizes the need for further research to better understand the physiological and psychological factors related to IPV-BI.

Studies that aim to evaluate outcomes after severe traumatic brain injury (TBI) must account for patients who die after withdrawal of life-sustaining treatment (WLST). If we are willing to assume that some of the patients who die of WLST might have had a good outcome at 6 months, the choice of analytic approach may impact the results. In this study, 6-month clinical outcomes for patients with TBI were simulated under six different scenarios related to WLST. Each scenario represents different assumptions related to the decision to choose WLST and how that decision relates to the 6-month clinical outcome. For each simulated dataset and scenario, three analytic approaches were used to estimate the probability of a good outcome at 6 months: complete case analysis, worst-case imputation, and inverse probability weighted analysis. The bias of the estimate from each of the approaches was used to compare the performance of the analysis approaches. When the probability of WLST was equal for all patients (i.e., covariates were not factored into the WLST decision), both the complete case analysis and the inverse probability weighted analysis were unbiased. When only patients who would have a poor outcome at 6 months were eligible to have WLST, only the worst-case imputation analysis was unbiased. When the probability of WLST was a function of observed patient characteristics that were also related to 6-month outcome (e.g., age, injury severity), only the inverse probability weighted analysis was unbiased. Finally, when the probability of missingness was related to an unobserved patient characteristic, none of the approaches were unbiased. If some patients who die of WLST might have had a good outcome, inverse probability weighting could be considered to decrease bias associated with censoring or imputing poor outcomes for participants with WLST.

Spinal cord injury (SCI) triggers an inflammatory response that is partially mediated by the inflammasome and the production of pro-inflammatory cytokines. We have previously shown that pannexin-1 is involved in the activation of the inflammasome, and that probenecid inhibits this caspase-1-mediated inflammatory process. In this study, we employed an in vivo model of contusive SCI to investigate the therapeutic effect of acute probenecid administration on histopathological and functional outcomes following SCI. Adult female Fischer rats (n = 46) underwent moderate thoracic SCI produced by dropping a 10 g weight from a height of 12.5 mm onto the exposed cord at T9, assigned three different groups, PBS administration group, and 1, 10, 100 mg/kg probenecid group, those were injected subcutaneously 15 min and 12 h after SCI. The sham group (n = 11) was the group that only had a laminectomy and did not have SCI. Histopathological analysis by Luxol Fast Blue/hematoxylin and eosin staining revealed that the penumbra volume was significantly reduced in the probenecid 100 mg/kg group compared with the PBS group. CatWalk gait analysis was performed at 7 weeks after SCI, which showed significant differences in coordination between the PBS and the probenecid 100 mg/kg-treated groups. Acute administration of probenecid after SCI resulted in the preservation of penumbra formation and coordination function in a thoracic SCI rat model. This report suggests that probenecid, an inhibitor of pannexin-1, has the potential to prevent secondary injury after SCI and improve outcomes following SCI.

Concussions remain the leading form of traumatic brain injury. Despite this, there is a paucity of pharmacologic and evidence-based treatments. The objective of this study was to investigate the benefit of Ghrelin (OXE-103) as a novel treatment for subacute concussion. The study consisted of an open-label treatment arm (OXE-103) with a nontreatment concurrent control arm receiving standard of care (SOC-only). Participants had a documented concussion, within 28 days of injury, and a Post-Concussion Symptom Scale (PCSS) of 20 or more. A total of 19 subjects completed the study: 13 treatments and 6 SOC. Treatment consisted of OXE-103 40 μg/kg twice daily by self-injection for 14 days. Main Outcome Measures were change in PCSS and Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS). Outcome measures were assessed at days 1, 4, 8, 11, 15, 21, and 44. A secondary outcome was 20% improvement on either which was considered a clinically meaningful response. We found a decrease in PCSS from baseline with OXE-103 (median -34 [interquartile range {IQR}: -44, -24]) at day 44 versus SOC (median -7 [IQR: -22, 16]) at day 44. We also found an improvement in QOLIBRI-OS from baseline with OXE-103 (median 21 [IQR: 12.5, 50]) at day 44 versus SOC (2 [IQR: -25, 20.8]) at day 44. 85% (95% confidence interval [CI]: 53, 98) of subjects treated with OXE-103 had a clinically meaningful response at day 44 on PCSS versus 33% (95% CI: 4, 78) of subjects in the SOC arm. When looking at improvement in QOLIBRI-OS, 85% (95% CI: 53, 98) of subjects treated with OXE-103 had a clinically meaningful response at day 44 versus 33% (95% CI: 4, 78) in the SOC arm. We conclude that subjects treated with OXE-103 showed improved PCSS and QOLIBRI-OS scores compared to those receiving only standard therapy. We recognize the limitations of this study, including small sample size and lack of randomization. The results indicate that OXE-103 is a potential therapeutic agent to treat patients with ongoing concussion symptoms. A larger, multicenter, randomized, placebo-controlled trial would be an important next step.

Repeated blast traumatic brain injury (rbTBI) is linked to dementia risk, potentially due to abnormal tau accumulation, although a definitive causal relationship remains elusive. This study aims to develop a model of rbTBI-induced tauopathy. We utilized wild-type (WT) rats and rats that are heterozygous for the mutated P301S human tau gene (Tg12099 +/-), the presence of which increases the propensity to develop tau neuropathology. At 2-3 months of age, rats were exposed to five blasts using the Advanced Blast Simulator or sham procedures. Behavioral and histological outcomes were evaluated at 10 and 15 months post-injury, respectively. The open field test revealed increased activity in blast-injured animals compared with sham. Tg12099 +/- females exhibited greater travel distances than WT females, while male activity levels did not differ by genotype. The novel object recognition test indicated impaired recognition memory in blast-injured animals, which was unrelated to genotype. There was a greater accumulation of phosphorylated tau in several brain regions of Tg12099 +/- rats compared with WT rats, yet no observable blast injury effect. Blast did not alter astro- and microgliosis, but increased astrogliosis was observed in Tg12099 +/- rats compared with WT rats in a region-dependent manner. We observed sex-dependent changes in microgliosis within the Tg12099 +/- group, with male Tg12099 +/- rats exhibiting increased IBA1 immunostaining compared with females. No such sex difference was observed in WT rats. Our findings suggest that while rbTBI can induce persistent behavioral deficits in rats, it does not exacerbate neuropathology in Tg12099 rats.

For nearly 350 years, the process of disseminating scientific knowledge has remained largely unchanged. Scientists conduct experiments, analyze the data, and publish their findings in the form of scientific articles. Since the turn of the century, this process has been challenged by numerous open science and data sharing efforts to enhance transparency, reproducibility, and replicability of scientific research. Big data approaches, together with machine learning and artificial intelligence, are frequently used to gain insight into the ever-growing complexity of biological systems and biomedical research. To utilize these approaches and harness the continuously increasing computational power requires data to be both machine readable and, ideally, harmonized across studies. Therein lies the challenge: understanding how to organize and describe data is a critical skill for scientists, yet one that is rarely explicitly taught. Common data elements (CDEs), standardized definitions, and reporting structures for data represent a practical solution to this challenge. With the goal of creating a common language to describe and share pre-clinical spinal cord injury (SCI) research data, the open data commons for SCI, in collaboration with the National Institute of Neurological Disorders and Stroke, kicked off this process with the "Preclinical SCI Common Data Elements (CDE) Workshop," held in conjunction with the National Neurotrauma Symposium in San Francisco, California in June 2024. In this report, we discuss the workshop proceedings, summarize the input provided by the SCI research community, share insights from related CDE efforts, and provide a pragmatic approach to creating CDEs for pre-clinical SCI research.

The objective of this study was to document the resolution rate of mild Traumatic Brain Injury (mTBI) symptoms at various time points in a nonathletic adult population and identify prognostic factors influencing recovery. Sixteen prospective cohort studies were included, focusing on participants aged 18-65 with acute mTBI, followed for a minimum of 1 month. The recovery criterion was the resolution of symptoms not attributable to pre-existing conditions. Risk of bias was assessed using the Quality in Prognostic Studies tool, with most studies rated as moderate risk, highlighting variability in methodological rigor. Symptom resolution was reported in 49.0% to 69.5% of patients at 1 month, 40.8% to 84.4% at 3 months, 38.3% to 72.2% at 6 months, and 58.1 to 68.3% at 12 months. These findings emphasize the first 6 months as a critical period for evaluating the risk of symptom chronicity. The most commonly reported prognostic factors was baseline symptom severity, including higher intensity of symptoms such as headaches, nausea, and dizziness, as well as elevated scores on validated symptom scales. Psychiatric history, such as pre-existing anxiety or depression, was also a significant predictor of prolonged symptoms. Biomarkers, including NSE and S-100B levels, and reduced blood-derived neurotrophic factors, were associated with poorer recovery at 6 months. Demographic factors, including age, gender, and education level, showed mixed results. While some studies associated female gender, older age, and lower education with poorer recovery, others found no significant correlations. These discrepancies highlight the complexity of mTBI prognosis. Overall, more than half of patients recover within 6 months, but persistent symptoms can have a profound impact on quality of life and functional status. Identifying patients at higher risk of prolonged recovery is crucial for targeted management strategies, emphasizing the importance of individualized, evidence-based care in mTBI populations.

Traumatic Brain Injuries (TBIs) are known to cause a myriad of symptoms in patients. One common symptom after injury is sleep disruptions. One neuropeptide system has been studied repeatedly as a potential cause of sleep disruptions after TBI- the orexin/hypocretin system. Orexin promotes wakefulness and arousal while disrupting the orexin system causes increased sleepiness and narcolepsy. Studies of TBI in human and animal subjects have shown that TBI affects the orexin system. This review serves as an overview of how TBI affects the orexin/hypocretin system, including structural and functional changes to the neurons after injury. This review is the first to include studies that examine how TBI affects orexin/hypocretin receptors. This review also examines how sex is accounted for in the studies of the orexin system after TBI.

Traumatic brain injury (TBI)-related growth hormone deficiency is often undertreated, despite documented physical, metabolic, and neuropsychiatric effects. Insulin-like growth factor (IGF-1), with neuroreceptors located in brain regions responsible for learning, memory, and mood, regulates cerebral blood flow, neurogenesis, and neuroplasticity. The aim of this study was to determine associations between IGF-1 levels and post-TBI symptom severity, anxiety, and depression. This retrospective observational study at an Academic Brain Injury Center included participants evaluated 3-12 months post-TBI with available IGF-1 values and complete Rivermead Post-Concussion Symptoms Questionnaire (RPQ-13), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) responses. Patients under 18 or over 65 and those with incomplete data were excluded. Participants were grouped by TBI severity: mild (Glasgow Coma Scale [GCS] 13-15) and moderate-to-severe (GCS < 13). IGF-1 Z-scores were standardized for age and gender. Significant negative correlations were found between IGF-1 levels and RPQ-13, GAD-7, and PHQ-9 scores across all TBI severity groups, with lower IGF-1 Z-scores correlating with higher symptoms of TBI, depression, and anxiety. The Generalized Linear Models showed that the IGF-1 Z-score is a significant predictor for GAD-7, PHQ-9, and RPQ-13. Specifically, a one-point increase in the IGF-1 Z-score is associated with a 29.85% decrease in anxiety symptoms on the GAD-7, a 16.30% reduction in depression severity on the PHQ-9, and a 39.23% decrease in post-TBI symptom severity on the RPQ-13. Findings suggest that decreased IGF-1 is associated with increased post-injury symptom severity, depression, and anxiety. Future studies should explore IGF-1 as a biomarker for TBI symptom severity.

Head trauma accompanied by circulatory failure is a rare but severe condition, and few reports regarding its prognosis or initial treatment strategies have been published. We aimed to evaluate the prognostic factors and treatment strategies for patients with head trauma and vital signs of shock. We included 415 consecutive patients with head trauma (Abbreviated Injury Scale [AIS] score ≥3) who were transported to our institution from January 2017 to December 2023. These patients were divided into shock and non-shock groups. Data on their background, vital signs at presentation, trunk injury status, surgical intervention, and hematological findings were examined. A retrospective analysis was conducted with the modified Rankin Scale score after 3 months as the primary outcome. The patients' mean age was 53.9 ± 24.4 years, 304 (73.3%) were male, 265 (63.9%) experienced severe trauma (injury severity score ≥16), 124 (29.9%) had multiple trauma (AIS score ≥3 at two or more locations), and 59 (14.2%) had accompanying vital signs of shock (shock index >1). Multivariable analysis revealed that older age (p < 0.0001), a lower Glasgow Coma Scale (GCS) score (p < 0.0001), elevated D-dimer levels (p = 0.0077), and pupillary abnormalities (p = 0.038) were independently associated with a poor prognosis in the non-shock group. In the shock group, older age (p = 0.0037) and neurosurgical intervention (p = 0.012) were independent prognostic factors. In contrast to those in the non-shock group, the GCS score and D-dimer levels were not useful prognostic factors in the shock group. The optimal cut-off age for prognosis was 64 years (area under the receiver operating characteristic curve: 0.752; sensitivity: 0.670, specificity: 0.777). The prognosis was significantly worse in the shock group when neurosurgery was required, suggesting that developing a treatment strategy aimed at more rapidly reducing intracranial pressure is essential, especially for patients under 64 years old with circulatory failure.