Neurotrauma reports最新文献

Traumatic brain injury is a world-leading cause of disability. Current treatments are not sufficient to promote neurological recovery. Intracerebral transplantation of allogeneic mesenchymal stem cells, specifically SB623, has shown promise in achieving better neurological recovery compared with a sham surgery group in the STEMTRA trial. However, the optimal location for cell transplantation remains unclear, as transplanted lesions vary between patients. This study aimed to explore the relationship between functional recovery and the location of transplanted lesions. This study included all Japanese subjects from the STEMTRA trial who were assigned to the cell transplantation group. Functional recovery was assessed by the difference in Fugl-Meyer Motor Scale (FMMS) scores between the screening period and 24 or 48 weeks post-transplantation. An FMMS score improvement of >8 was defined as an improved group. Lesions responsible for motor deficits were categorized into three groups: motor cortex (Cortex), deep white matter (DWM), or both (Cortex and DWM). Data on the 15 transplanted sites per patient were obtained from surgical navigation software, and the distance from the damaged area to the transplanted sites was calculated. Twelve patients were included in this post-hoc analysis. No patients in the 2.5 × 10⁶ cells group showed improvement and were therefore excluded from further analysis. Five patients were categorized into the Cortex group and four into the DWM group. The distance between the transplanted site and the injury point ranged from 0 to 39 mm. A moderate to strong trend of correlations was observed, suggesting that a shorter distance is preferable for the motor cortex group, while a greater distance is preferable for the DWM group. The optimal site for stem cell transplantation may be different from the damaged site of the patient; however, a further large number cohort is necessary to elucidate this hypothesis.

Exercise to treat traumatic brain injury (TBI) is a novel approach that has only become recognized in the past decade. High-intensity gait training (HIGT) has been studied in subjects following stroke; however, little research investigates similar protocols on patients with TBI. The study evaluated HIGT as an intervention for enhancing patient recovery after TBI. Adult subjects (18-65 years) who suffered TBI were randomly allocated to an intervention (HIGT) or control (low-intensity physical therapy) group given three days/week for 1 h over four weeks. Assessments included the 10-m walk test, 6-min walk test, Berg Balance Scale, five-times sit-to-stand (5TSTS), timed up and go (TUG), cognitive TUG, and Montreal Cognitive Assessment (MoCA) at day one, two weeks, four weeks, and a four-week follow-up. In addition to a trend toward improved gait speed (p < 0.1) and significantly improved endurance (p < 0.05) in the HIGT group (n = 5), both the control (n = 4) and HIGT groups demonstrated trends toward improved mobility (5TSTS, p < 0.1; TUG, p < 0.1) and significantly improved cognition (cognitive TUG, p < 0.01; MoCA, p < 0.05) over the four-week time period and at the one-month follow-up. HIGT showed longer-lasting rehabilitative effects on gait distance, endurance, mobility, and cognitive function at the four-week follow-up. This study suggests that HIGT may support functional recovery, and future work will involve increasing sample size.

Traumatic brain injury (TBI) results in changes in brain networks followed by long-lasting behavioral and social impairments. This study explores the relationship between neurobehavioral as well as physical function deficits and structural changes in brain white matter (WM) and gray matter (GM) in individuals with TBI by evaluating morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data. The structural MRI-based fractal analysis has emerged as a promising new approach to measure the morphology of the WM and GM. While DTI metrics reflect the microstructural properties of WM, the fractal dimension (FD) is regarded as a measure of morphometric complexity of the system, thus providing complementary information on the brain structure. This study included 10 individuals having moderate-to-severe TBI with balance/postural control deficits and 8 healthy controls. The network-based GM and WM morphologies were measured using FD and structural connectivity metrics, and fractional anisotropy (FA) was assessed using DTI in major WM tracts. The associations between brain structural (FA and FD) measures and a number of neuropsychological assessment and sensorimotor function outcomes were evaluated using partial least square correlation analysis. Our findings showed that the complexity in GM of default mode network, salience network, sensorimotor network, and frontoparietal network is positively correlated with the performance in cognitive and balance outcomes in patients with TBI. On the contrary, in DTI connectivity measures, only few regions including corona radiata, inferior longitudinal fasciculus, and middle cerebellar peduncle were strongly correlated with the behavioral outcomes in the TBI group. Our study suggests that the brain structure complexity measured by FD is a promising and complementary approach to DTI for potentially serving as a biomarker of cognitive and sensorimotor functions in TBI population.

Face cooling (FC) initiates the mammalian dive reflex, which elicits a parasympathetic autonomic response. In our pilot study, collegiate athletes had a blunted parasympathetic response to FC within 10 days of sport-related concussion (SRC). The objective of the current study was to assess the FC response in adolescent athletes with acute SRC and after clinical recovery. Symptomatic adolescents with SRC (n = 23, 15.48 ± 1.2 years, 52% male) had heart rate (HR) and blood pressure (BP) measured during the FC test (7.83 ± 2.5 days since injury) and again after clinical recovery (46.44 ± 36.4 days later). Controls (n = 24, 15.83 ± 1.6 years, 58% male) performed the same assessments twice (48.00 ± 18.9 days apart). The main outcome measures were the rate of change in HR and HR variability (HRV) during the first 2 min of FC. Throughout FC, we found no significant differences between groups at the initial visit in the rate of change for HR (mean difference = 2.58 [-0.33, 5.50] bpm/min, p = 0.082), mean arterial BP (-0.02 [-3.49, 3.45] mmHg/min, p = 0.990), root mean square of successive differences (-13.46 [-34.02, 7.10] ms/min, p = 0.197) or low to high-frequency ratio (0.24 [-0.77, 1.25], p = 0.637). We also found no differences in our main outcome measures among concussed adolescents with delayed recovery (n = 10) compared with those with normal recovery (n = 13). A history of prior concussion had a significant effect on the HR and HRV responses to FC, suggesting that SRC may have prolonged effects on the autonomic nervous system (ANS). We conclude that acutely concussed adolescents do not differ from controls in parasympathetic response to FC acutely or upon recovery but that a history of concussion affects this response. We recommend that future studies control for concussion history when investigating the ANS in concussed adolescents.

Adolescents who have sustained a concussion or mild traumatic brain injury (mTBI) are prone to repeat injuries which may be related to subtle motor deficits persisting after clinical recovery. Cross-sectional research has found that these deficits are associated with altered functional connectivity among somatomotor, dorsal attention, and default mode networks. However, our understanding of how these brain-behavior relationships change over time after clinical recovery is limited. In this study, we examined categorical and dimensional trajectories of functional connectivity and subtle motor performance in youth clinically recovered from mTBI and never-injured controls (10-17 years). All participants completed task-based and resting-state functional magnetic resonance imaging scans and the Physical and Neurological Examination of Subtle Signs (PANESS) at initial and 3-month follow-up visits. We examined somatomotor-dorsal attention and somatomotor-default mode network connectivity and their association with PANESS performance. Compared with controls, a larger proportion of youth recovered from mTBI showed increases in somatomotor-dorsal attention functional connectivity over time; in contrast, there were no differences in somatomotor-default mode connectivity trajectories between youth recovered from mTBI and controls. Relative to controls, youth recovered from mTBI who showed greater increases in somatomotor-dorsal attention connectivity over time also completed motor tasks more slowly at the 3-month compared with the initial visit. Collectively, these findings suggest that longitudinal changes in somatomotor-dorsal attention functional connectivity may be associated with lingering motor learning deficits after clinical recovery from pediatric mTBI. Further research is necessary to understand how trajectories of functional connectivity and motor performance can inform individual-level outcomes, for instance, susceptibility to future injuries in both youth who are never injured and those clinically recovered from mTBI.

Mild traumatic brain injury (mTBI) accounts for 80% of all TBI, may be associated with chronic impairments, and is difficult to diagnose due to a lack of objective markers. In this study, we investigated whether neurosteroids can serve as blood biomarkers for mTBI. Two cohorts of C57BL/6 mice were subjected to a model of mTBI combining impact with rotational acceleration or sham surgery. The first cohort underwent neurological testing for anxiety, balance, and locomotion before and after mTBI. For the second cohort, brains and plasma were collected 6 or 24 h after mTBI to measure steroid and neurosteroid levels by gas chromatography-tandem mass spectrometry. Traumatized mice exhibited significantly prolonged wake-up time from anesthesia, transiently increased beam-walk time, and mild astrogliosis compared with their control counterparts, but did not suffer from skull fractures, intracranial hemorrhage, or mortality. Isopregnanolone and 3β,5α-tetrahydrodeoxycorticosterone (ISODOC) were significantly decreased by more than 50% in brain parenchyma at 6 and 24 h after mTBI, while ISODOC was also significantly decreased in plasma (-75%). Therefore, ISODOC may be a candidate diagnostic biomarker for mTBI.

Nationally representative associations of social determinants of health (SDoH) and health care access metrics with TBI-related mortality are not well described and may differ by age. Using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiological Research platform and other publicly available datasets, we investigated correlations between county-level measures of SDoH (multidimensional deprivation index, social deprivation index, rural-urban continuum codes) and health care access (median distance to nearest emergency department, trauma center, intensive care unit [ICU], number of hospitals and number of hospitals with ICU capability per 1,000 population) with county-level TBI-related mortality overall and stratified by age in the United States from 1999 through 2020. Data from 2,970 counties (95.4% of eligible U.S. counties) were included. We observed a modest correlation of higher county-level TBI-related mortality with greater rurality (ρ = 0.54, 95% CI = 0.52-0.57, R ² = 0.30). Higher county-level TBI-related mortality was also modestly correlated with farther county-level median distance to nearest hospital with ICU capability (ρ = 0.43, 95% CI = 0.39-0.46, R ² = 0.18). Correlations with SDoH and health care access measures were stronger for county-level TBI-related mortality among younger (aged <50 years) compared to among older (aged ≥75 years) individuals. In conclusion, rurality and access to hospitals with ICU level care are correlated with county-level TBI-related mortality, with rurality accounting for 30% of the observed variance in county-level TBI-related mortality. Rural communities with limited access to ICUs should be targeted for prevention efforts of TBI-related deaths among younger individuals, while additional work is needed to determine factors related to variation in TBI-related mortality among older individuals.

Autonomic regulation of cardiovascular function is often disrupted following a spinal cord injury (SCI). A systematic review was undertaken to evaluate the effect of non-invasive, non-pharmacological (NINP) interventions on cardiovascular autonomic biomarkers in adults with SCI. AMED, CENTRAL, CINAHL EMBASE, and MEDLINE were searched from inception to May 17, 2024. Randomized controlled trials (RCTs) of NINP interventions for cardiovascular autonomic biomarkers (heart rate variability [HRV], systolic blood pressure variability [SBPV], or baroreflex gain) in adults (≥18 years of age) with SCI (>3 months) were included. Primary outcomes included HRV (low-frequency power [HRV-LF], high-frequency power [HRV-HF], root mean square of successive differences [RMSSD]), SBPV (low-frequency power [SBPV-LF]), and baroreflex sensitivity. The quality and certainty of the evidence were assessed using version 2 of the Cochrane risk of bias tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis tool, respectively. Of 2651 records identified, six RCTs were included (participants, n = 123). HRV-LF (four studies; participants, n = 69) and HRV-HF (five studies; participants, n = 93) showed no to small changes in favor of NINP interventions ([g = 0.25; 95% confidence interval [CI] = -0.23, 0.73; p = 0.31; I² = 0%], [g = 0.00; 95% CI = -0.41, 0.42; p = 0.98; I² = 0%], respectively). Limited evidence was available for RMSSD, SBPV-LF, and baroreflex gain. This review found that the evidence is inconclusive regarding the effect of NINP interventions on the included HRV, BPV, and BRS parameters in adults with SCI. Further research with strong methodological rigor is needed to provide greater insights in this area.

Iraq and Afghanistan War-era Veterans are at elevated risk for physical injuries and psychiatric illnesses, in particular the polytrauma triad of mild traumatic brain injury (mTBI), post-traumatic stress disorder (PTSD), and chronic pain. The gut microbiome has been implicated in modulation of critical processes beyond digestion, including immune system functioning and stress responsivity, and may be an important factor in understanding physical and mental health outcomes following deployment and trauma exposure. However, minimal research to date has sought to characterize gut microbiome composition in this population. Male Veterans of the conflicts in Iraq and Afghanistan who previously completed a Veterans Affairs' comprehensive TBI evaluation were enrolled in the current study. Participants completed self-report measures of PTSD symptom severity, pain intensity and interference, fatigue, cognitive symptoms, substance use, and sleep quality. They also submitted fecal samples, and metagenomic sequencing was used to calculate alpha and beta diversity and taxonomic microbial composition. Associations between microbiome data and clinical variables were then examined. Alpha and beta diversity measures were not significantly correlated with clinical outcomes. Fatigue, post-concussive symptoms, executive function symptoms, and cannabis use were associated with differences in gut microbial composition, specifically Verrucomicrobiota. Together, results suggest that altered gut microbiome composition is associated with psychiatric and cognitive symptoms in Veterans and highlight a potential new therapeutic target of interest. Future research is needed to examine whether probiotic treatment is effective for reducing symptoms common in this clinical population.

This study aims to describe the late clinical outcomes of patients with severe traumatic brain injury (sTBI) and the risk factors associated with it. Patients were enrolled between April 2012 and January 2015 and followed until January 2022. The inclusion criteria were age 16-65 years, Glasgow Coma Scale ≤8 on admission, diagnosis of blunt TBI with Marshall diffuse injury type II on initial computerized tomography (CT), and alive at discharge. Clinical, laboratory, and radiological data from admission were collected. Glasgow Outcome Scale Extended (GOSE), Functional Independence Measure, and Zarit Burden Interview (ZBI) were assessed in the follow-up. Sixty-five patients were included, with a median follow-up time of 8 years. Nineteen (29.2%) patients had good recovery (GOSE 7-8), and 10 (15.3%) had moderate-to-severe sequelae (GOSE 4-6). Thirty-six (55.4%) patients died after discharge, and most of them in the first 3 months after discharge (n = 26; 72.2%). Despite the early mortality rate being the highest, the 6-month score is explained in the text (CRASH-CT) score on admission was not associated with death in the follow-up (p = 0.25). In the multivariate statistical analysis, only prothrombin time was associated with GOSE (p = 0.01). Twelve (41.3%) patients were independent for basic activities of daily living, and the most common cause of dependence was memory impairment (n = 12; 41.3%). The median ZBI score reported by caregivers was 23.5 (range 5-48), indicating mild overload. In this study, patients with sTBI sustaining Marshall II lesions had a significant mortality rate after discharge, and we found coagulation impairment as a potential predictor of poor outcomes. Around 30% experienced functional dependence and inability to return to social and work activities. Current instruments used to predict outcomes of TBI patients had poor predictive performance in this low- and middle-income country population, suggesting the need for new models to properly guide clinical decision-making and counseling family members.