Neurotrauma reports最新文献

Repetitive, sub-concussive head impacts have been associated with increased chronic traumatic encephalopathy (CTE) incidence. CTE diagnosis traditionally relies on postmortem examination, which limits precise correlation between cause and effect. This prospective study embraced innovative diffusion magnetic resonance imaging, which enables in vivo quantification of acute, subacute, and chronic changes in brain tissue microstructure. This approach was used to evaluate changes in white matter microstructural status at intervals up to 180 days following a specified soccer heading protocol. This study was approved by university research ethics committees. Twelve adult males were recruited to the study and gave signed, informed consent. Six Intervention participants were university-level soccer players, with six Control participants drawn from university-level noncontact sports. Multi-shell diffusion-weighted MRI data were acquired on a 3T Siemens Connectom (300 mT/m) scanner using the HARDI protocols. Baseline measures of fractional anisotropy, mean diffusivity, and mean kurtosis were acquired at day 0. The Intervention cohort then performed 10 soccer "headers" in a laboratory, with acceleration-time data captured using an instrumented mouthguard and post-processed to report common metrics. The Intervention group was then re-scanned at day 1 (n = 6), day 90 (n = 5), and day 180 (n = 4). The Control group was re-scanned at day 1 (n = 6) and day 180 (n = 3). Many brain tracts were identified as having significant (p < 0.05) changes in white matter microstructural changes at day 90, which correlated strongly with the magnitude of head impact. A smaller number of tracts had changes at day 1 and day 180. These results indicate that, within this pilot population, the magnitude of repeated soccer headers appears to correlate with the magnitude of white matter microstructural change. Additional investigation is required to determine whether the effect of such an intervention influences long-term brain health risk.Board.

Early seizures within 1 week after traumatic brain injury (TBI) are classified as acute symptomatic seizures, which can worsen secondary brain injury, leading to poor neurological outcomes and increased mortality. Despite prophylactic antiepileptic drug (AED) use, early seizures remain prevalent, particularly in severe cases. This study aims to identify risk factors for early seizures in patients with TBI receiving prophylactic levetiracetam monotherapy and to develop a clinical scoring model for risk stratification. This study was conducted at an emergency medical center in Japan (2018-2022). In total, 168 patients with TBI were screened, and 147 severe cases met eligibility criteria. Exclusion criteria included age under 18, prehospital cardiac arrest, prior AED use, pregnancy, and alcohol dependency. All patients received prophylactic levetiracetam, with dosage and duration determined by neurocritical care physicians. The primary outcome was early seizures and associated risk factors. Secondary outcomes included hospital stay, functional outcomes, and in-hospital mortality. Multivariate logistic regression identified independent risk factors, and a clinical risk scoring model was developed. Early seizures occurred in 25 of the 147 patients. Multivariate analysis identified heart rate (odds ratio [OR]: 1.048, p < 0.001), creatinine level (OR: 1.535, p = 0.026), and acute subdural hematoma (OR: 5.861, p = 0.027) as independent risk factors. A clinical risk scoring model incorporating these variables demonstrated high predictive accuracy (area under the receiver operating characteristic curve: 0.828, 95% confidence interval: 0.725-0.931). Patients scoring >4.5 underwent electroencephalographic monitoring. This study presents a novel risk scoring model integrating heart rate, creatinine, and acute subdural hematoma to predict early seizures in patients with TBI despite prophylactic levetiracetam use. The model enables rapid risk stratification upon admission and may guide targeted neurocritical management.

Neurotrauma can cause endothelial dysfunction, characterized by neurovascular barrier disruption, tissue edema, neuroinflammation, and coagulation abnormalities, all of which may contribute to secondary injuries and worsened clinical outcomes. Here, we assess the effect of different types of neurotrauma on the local levels of biomarkers of endothelial injury and inflammation. Cerebrospinal fluid (CSF) samples were collected at multiple time points from patients with isolated traumatic spinal cord injury (SCI) and patients with concomitant SCI and traumatic brain injury (TBI). CSF levels of analytes associated with endothelial damage, as well as inflammatory mediators, were measured. Compared with patients with isolated SCI, those with SCI + TBI demonstrated significantly elevated CSF levels of multiple biomarkers linked to endotheliopathy and inflammation. In the presence of TBI, the highest increases in CSF levels of endothelial markers were observed for matrix metalloproteinase 10 (MMP-10), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). Among inflammatory factors, thymic stromal lymphopoietin (TSLP) showed the most pronounced difference in CSF content in patients with SCI + TBI compared with those with SCI alone, followed by interferon α2 (IFNα2) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, CSF levels of MMP-1, MMP-10, VEGF-A, IFNα2, and TSLP significantly correlated with injury severity score. Our findings indicate that, in the presence of concomitant TBI, patients with SCI exhibit higher CSF levels of biomarkers associated with endotheliopathy, blood-brain barrier breakdown, protease-mediated degradation of endothelial glycocalyx, and neuroinflammation. These results identify potential theranostic biomarkers to stratify high-risk patients and mitigate neurovascular damage, thereby improving clinical outcomes.

Traumatic brain injury (TBI) can lead to cognitive dysfunction, with underlying mechanisms poorly understood. Interleukin (IL)-6, particularly via soluble IL-6 receptor (sIL-6R) trans-signaling, can exacerbate neurodegeneration. Soluble glycoprotein (sgp)130 inhibits this pathway, reducing neuroinflammation and improving cognition in a mouse TBI model. In this study, we evaluated sgp130Fc on cognitive recovery and neural damage using a severe controlled cortical impact (CCI) injury model in rats. Male rats (N = 37) underwent CCI (6-mm flat-tip impactor; 4.0 m/sec; 2.8 mm deformation) or sham procedures and received sgp130Fc (10 mg/kg) or vehicle (VEH) intraperitoneally every 3 days starting 1 day post-injury (dpi). Motor function (beam walk and balance; 1-7 dpi), and spatial learning and memory (Morris water maze [MWM], 14-19 dpi) were assessed using a repeated measures analysis of variance followed by a Tukey's post hoc analysis. Lesion volume was assessed (21 dpi) using a two-tailed t-test. CCI rats exhibited transient motor deficits not influenced by sgp130Fc. CCI + VEH rats had longer latencies and path lengths to the submerged platform versus shams (p < 0.05). On 18 dpi, CCI + sgp130Fc rats had shorter latencies (p = 0.04) and path lengths (p = 0.02) versus CCI + VEH rats. CCI + VEH rats displayed more inefficient swim strategies than CCI + sgp130Fc rats. CCI + VEH, but not CCI + sgp130Fc rats, had significantly worse performance on the MWM visible platform trials, particularly with respect to path length, suggesting, along with the swim strategy data, possible benefit with spatial navigation when the platform is utilized as a proximal cue. sgp130Fc did not significantly reduce lesion volume. These findings support sgp130Fc as a potential therapeutic for cognitive recovery following TBI.

Traumatic spinal cord injury (TSCI) can cause significant and permanent disability. For over 20 years, lumbar cerebrospinal fluid (CSF) drainage has been routinely performed during the surgical repair of thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. However, intrathecal CSF drainage has not been adequately evaluated in the setting of acute TSCI. This living systematic review sought to evaluate whether intrathecal catheter CSF drainage to reduce intrathecal pressure (ITP) in the acute postinjury phase was safe and feasible and could improve clinical indices and neurological recovery in patients with acute TSCI. A literature search of PubMed/MEDLINE, Ovid Medline, CINAHL, and Cochrane Database of Systematic Reviews from database inception to March 2024 yielded 1007 potentially relevant articles, 806 were excluded based on title and abstract search and 147 articles underwent full article review. There were two randomized controlled studies, and one cohort study included in the review. Sample sizes ranged from 11 to 22 patients with an age range of 23-67 years. Drains were placed at different times postinjury in each study, with a range of 10-72 h. In the first study, open CSF drainage was used to decrease ITP to 10 mmHg (limit of 10 mL/h). The second study used periodic drainage with up to 10 mL of CSF drained each time (maximum of 30 mL/day). The third study used an open, less restrictive CSF drainage with a target ITP of <10 mmHg. Mean arterial blood pressure and spinal cord perfusion pressure were measured in all three studies. One study evaluated direct intraspinal pressure monitoring. Despite small sample sizes, the three studies demonstrated that intrathecal CSF drainage through a lumbar catheter was feasible and safe acutely after TSCI. Additionally, the results suggest an overall improvement in spinal cord perfusion acutely and trends toward improvements in neurological recovery. There is an important need for much larger prospective trials to evaluate CSF drainage together with other treatment and monitoring strategies to optimize care and improve outcomes. Innovative clinical trial designs could more efficiently evaluate multimodal treatments.

Traumatic brain injuries (TBIs), particularly contusive types, are associated with disruptions in neuronal communication due to focal and diffuse axonal injury, as well as alterations in the neuronal chemical environment. These changes can negatively impact neuronal networks beyond the primary injury site. In this Translational Outcomes Project in NeuroTrauma UG3 phase study, we sought to use multimodal neuroimaging biomarker approach to assess functional connectivity and brain tissue microstructure, along with T2 relaxometry, in two experimental rat models of TBI: controlled cortical impact (CCI) and lateral fluid percussive injury (LFPI). Rats underwent imaging using an 11.1 Tesla scanner at 2 and 30 days post-injury. Naïve controls were scanned once to establish baseline comparisons for both TBI groups. Imaging modalities included functional magnetic resonance imaging (fMRI), diffusion-weighted imaging (DWI), and multi-echo T2 imaging. fMRI data were analyzed to evaluate functional connectivity across lateral and medial regions of interest in the cortical mantle, hippocampus, and dorsal striatum. DWI scans were used to generate maps of fractional anisotropy (FA) and mean, axial, and radial diffusivities, focusing on cortical and white matter (WM) regions near the injury epicenter. Our findings revealed significantly increased contralateral intracortical connectivity at 2 days post-injury in both CCI and LFPI models, localized to similar cortical areas. This increased connectivity persisted at day 30 in the CCI model but not in LFPI. Changes in WM and cortical FA and diffusivities were observed in both models, with WM alterations predominating in CCI and cortical changes being more pronounced in LFPI. These results highlight the utility of multimodal MRI for characterizing distinct injury mechanisms in contusive and skull-penetrating TBI models.

Traumatic brain injury (TBI) is associated with significant deficits across cognitive, emotional, and somatic functions, contributing to reduced quality of life for TBI survivors. Synaptic vesicle cycling, crucial for neurotransmitter release, involves a tightly regulated process of exocytosis and endocytosis, of which monomeric alpha-synuclein (mAS) is implicated in both, and therefore, may underpin neurotransmission impairments post-TBI. Our team previously demonstrated that controlled cortical impact (CCI) reduces hippocampal and cortical mAS in the weeks postinjury. We hypothesized that genetic knockout (KO) of mAS expression may exacerbate TBI-induced deficits in neurobehavioral performance and synaptic health. To elucidate the role of AS in neurobehavioral recovery and histopathological alterations post-TBI, we employed a genetic AS-KO mouse model (B6;129X1-Snca/J). Markers of exocytosis and endocytosis, cysteine-string protein alpha (CSPα) and clathrin light chain (CLC), respectively, and the astrocytic marker glial fibrillary acidic protein (GFAP) were assessed. Male AS-KO and wild-type (WT) littermate controls received 1.8 mm CCI or Sham control surgery (Sham-WT, CCI-WT, CCI-KO, n = 10/group). Beam balance testing (1-5 days) did not reveal differences in balance latency between groups. Spatial learning (Morris water maze, 9-13 days) was significantly impaired in both CCI groups relative to Sham-WT controls, whereas the CCI-KO mice performed comparably to Sham-WT mice in spatial memory testing. Following CCI, GFAP expression was significantly elevated in the ipsilateral hemisphere, independent of genotype, compared to Sham controls. CCI also resulted in a reduction of CLC expression in the ipsilateral hemisphere, while CSPα expression remained unchanged in both hemispheres across all groups.

Insomnia and depression are common co-morbidities associated with mild traumatic brain injury (mTBI). Data from Transforming Research and Clinical Knowledge in TBI, a longitudinal cohort study of TBI and orthopedic controls (OTC), were used to examine insomnia trajectories and the temporal relationship between insomnia and depressive symptoms during recovery. mTBI (n = 1,557) and OTC (n = 226) adult patients with no psychiatric or sleep disorder history were assessed at 2 weeks and 3, 6, and 12 months post-injury, and at three long-term assessments between 2 and 10 years post-injury. Latent class growth analysis identified five insomnia trajectory classes during the first year post-injury, revealing 25% with persistent insomnia, 4% improving, and 71% below the clinical cutoff. A random intercept cross-lagged panel model tested the lagged effects between insomnia and depression. In addition to being longitudinally correlated (φ = 0.74, p < 0.001), depressive symptomatology operated as a leading indicator of worsening insomnia from 3 to 6 months post-injury (β = 0.20, p = 0.001) across the whole sample. The multigroup model revealed less insomnia (α = -0.31, p = 0.006) and depressive symptoms (α = -0.52, p < 0.001) in OTC relative to mTBI. From 1 to 5-10 years post-injury, mTBI low insomnia classes remained stable, while the highest class improved moderately (-5.50, 95% confidence interval: -7.84, -3.16, p < 0.001). Our findings suggest depressive symptoms may lead to worsening insomnia during the subacute recovery period and that a subset of patients with mTBI may suffer from new-onset insomnia that persists for more than 5 years.

Concussions or mild traumatic brain injuries (mTBI) are a frequent outcome of contact sports, and adolescents and young adults face a disproportionately higher risk of repeated injury. Prominent sequelae of mTBI observed in younger populations include anxiety, decreased sleep quality, insomnia, and impaired cognitive performance, all of which can extend beyond the acute phase of recovery. Although sleep is an essential aspect of the recovery process, few studies have evaluated the impact of mTBI on objective sleep measures, especially in younger athletes. The purpose of this systematic review was to analyze current literature on objectively measured sleep following mTBI. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, out of 2154 records, 17 studies were included, focusing on individuals aged 10-30 years, as they experience more sports-related concussions. Across 15 actigraphy and 2 polysomnography studies, results concerning total sleep time and sleep efficiency were mixed. However, several studies observed increased wake after sleep onset, a marker of sleep fragmentation, throughout mTBI recovery. Increased sleep fragmentation may explain frequently reported sleep complaints in this population and could ultimately contribute to a cycle of increasingly disrupted sleep. Additional research is needed to understand the relationship between mTBI and sleep, as sleep disruption during this critical period of neurocognitive development can have long-term impacts on brain health.

The optimal hemodynamic management of traumatic spinal cord injury (tSCI) is not well established. We performed a systematic review and meta-analysis of patients with acute tSCI to assess the role of lumbar cerebrospinal fluid drainage (CSFD) and to identify factors predictive of neurological improvement. Three studies involving 46 patients with acute tSCI, lumbar drain placement with CSFD, and available pre- and post-intervention American Spinal Injury Association (ASIA) Impairment Scale or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor scores were identified. One study was analyzed separately (Cohort A) using ASIA grade because post-intervention ISNCSCI motor scores were not reported. In the remaining two studies (Cohort B), two independent meta-analyses with meta-regressions were performed to determine the mean difference in ISNCSCI motor scores by CSFD and time to decompression. Individual patient data were used for all analyses. In Cohort A, there was no significant difference in ASIA grade before lumbar CSFD and at the last follow-up (Wilcoxon signed rank test: p = 0.130). In Cohort B, female sex and anterior decompression were associated with greater neurological recovery compared with male sex (p = 0.045) and a combined approach to decompression (p = 0.048), respectively. There were no other significant indicators of better motor scores in either cohort. CSFD with a target intrathecal pressure, rather than volume restrictions, may allow for sufficient fluid drainage to maximize spinal cord perfusion pressure (SCPP). Patients may benefit most from individualized management of SCPP because of the wide variance in interpatient and chronological intrathecal pressure.