Neurotrauma reports最新文献

The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 56 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from n = 21 patients with acute TBI. The resulting protein findings were then compared with CSF obtained by lumbar puncture from n = 14 patients with noninfectious CNS disorders comprising relapsing-remitting multiple sclerosis, anti-N-methyl-d-aspartate-receptor encephalitis, acute disseminated encephalomyelitis, and n = 14 patients with progressive multifocal leukoencephalopathy, herpes simplex encephalitis, and other types of viral meningitis. We also utilized n = 7 healthy controls (HCs). In the comparison between TBI and noninfectious inflammatory CNS disorders, concentrations of 55 proteins significantly differed between the groups. Among them, 23 and 32 proteins were up- and downregulated, respectively, in the TBI group. No proteins were uniquely identified in either group. In the comparison of TBI and HC, 51 proteins were significantly different, with 24 and 27 proteins being up- and downregulated, respectively, in TBI. Two proteins (fibrinogen gamma chain and transketolase) were uniquely identified in all samples of the TBI group. Also in the last comparison, TBI versus infectious inflammatory CNS disorders, 51 proteins differed between the two groups, with 19 and 32 proteins being up- and downregulated, respectively, in TBI, and no unique proteins being identified. Due to large discrepancies between the groups compared, the following proteins were selected for further deeper analysis among those being differentially regulated: APOE, CFB, CHGA, CHI3L1, C3, FCGBP, FGA, GSN, IGFBP7, LRG1, SERPINA3, SOD3, and TTR. We found distinct proteomic profiles in the CSF of TBI patients compared with HC and different disease controls, indicating a specific interplay between inflammatory factors, metabolic response, and cell integrity. In relation to primarily infectious or inflammatory disorders, unique inflammatory pathways seem to be engaged, and could potentially serve as future treatment targets.

Acute traumatic neural injury, known as traumatic brain injury (TBI), stands as a significant contributor to global mortality and disability. Ideally, continuously monitoring cerebral compliance/cerebral compensatory reserve would enable timely interventions and avert further substantial deterioration in TBI cases. RAP, defined as the moving Pearson's correlation between intracranial pressure (ICP) pulse amplitude waveform and ICP, has been proposed as a continuously updating index in this context. However, the literature remains scattered and difficult to navigate. Thus, the goal of this scoping review was to comprehensively characterize the literature regarding RAP and its association with (1) other multimodal cerebral physiological monitoring, (2) neuroimaging features, and (3) long-term patient outcomes. We subsequently conducted a systematic scoping review of the human literature to highlight the association of RAP with continuous multimodal monitoring of cerebral physiology, neuroimaging, and patient outcomes in the context of adult TBI patients. Our review encompassed 21 studies focusing on these topics. The primary findings involve meticulous analysis of studies, categorizing findings into three states of RAP to clearly understand its relation to cerebral physiology and clinical outcomes. State 1 signifies a healthy condition with a small positive value near zero (RAP <0.5). Conversely, state 2, a predominant characterization of TBI patients, indicates compromised compensatory reserve, featuring a large positive RAP value (RAP > 0.4). State 3 emerges in worsened conditions, showcasing further compromised compensatory reserve, exhausted cerebrovascular reactivity, and disturbed cerebral autoregulation. A substantial number of patients with fatal outcomes was found in state 3, marked by a notable occurrence of decreasing and, in some instances, negative RAP. The significance of this review lies in establishing a platform for future research directions to enhance the precision and clinical implications of RAP in TBI care, ultimately aiming to prevent the transition from state 2 to state 3 and mitigate fatal outcomes.

Research has found that service members (SMs) with mild traumatic brain injury (mTBI) and co-occurring bodily injuries endorse lower chronic postconcussive symptom severity than SMs with mTBI and no bodily injuries. Investigations were conducted with primarily post-9/11 war-era SMs with blast injuries. The current study explores these findings in a cohort of more heterogeneous and recently evaluated military SM. Possible reasons suggested for the earlier findings include SMs with bodily injuries report fewer postconcussive symptoms due to (1) focusing attention on extra-cranial injuries and associated pain; (2) receiving more interpersonal and medical support, lowering distress; (3) using analgesics such as morphine or opioids; or (4) experiencing delayed postconcussive symptoms. The current investigation evaluates each of these hypothesized reasons for the earlier findings and the generalizability of the findings to a more recent sample. Data were extracted from 165 SMs in a TBI repository at a U.S. military medical center. All participants reported a history of an mTBI, confirmed by a clinical interview to meet Veterans Affairs and Department of Defense criteria. Other bodily injuries received at the time of the mTBI were documented with the Abbreviated Injury Scale (AIS). Multiple regression models evaluated the ability of the four hypothesized mechanisms to predict postconcussive symptom severity, measured by the Neurobehavioral Symptom Inventory. SMs with bodily injuries (n = 48) reported nonsignificantly lower postconcussive symptoms than SMs with no bodily injuries (n = 117). The level of subjective pain was a determinant of postconcussive symptom severity among SMs with a history of mTBI, with or without associated bodily injuries. Social support was a weaker negative predictor of postconcussive symptoms among SMs with no associated bodily injuries.

The increasing incidence of traumatic brain injury (TBI) among older adults, particularly mild injuries from falls, underscores the need to investigate age-related outcomes and potential sex differences in response to TBI. Although previous research has defined an aging-TBI signature (heightened glial responses and cognitive impairment) in open-skull moderate-to-severe TBI models, it is unknown whether this signature is also present in mild closed-head injuries (CHIs). This study explores the influences of age and sex on recovery in a mouse CHI model induced by an electromagnetic impactor device in 4-month-old and 18-month-old C57BL/6 mice. We assessed the righting reflex, body weight, behavior (radial arm water maze and active avoidance), and inflammation (GFAP, IBA1, CD45) in the neocortex, corpus callosum, and hippocampus. We observed that aged female mice exhibited more severe TBI-induced cognitive deficits. In addition, a more pronounced reactive neuroinflammatory response with age was noted within white matter regions. Conversely, gray matter regions in aged animals either showed no enhanced pathological changes in response to injury or the aged mice displayed hyporesponsive glia and signs of dystrophic glial degeneration that were not evident in their younger counterparts following CHI. These findings suggest that aging influences CHI outcomes, partially reflecting the aging-TBI signature seen in more severe injuries in white matter, while a distinct aging and mild-TBI signature was identified in gray matter. The heightened vulnerability of females to the combined effects of age and mild CHI establishes a foundation for further investigation into the mechanisms underlying the sexually dimorphic response in aging females.

The presence of a calcified or ossified chronic cranial epidural hematoma (EDH) is rare and has been described in only a few case reports in the literature. Consequently, clear treatment strategies remain elusive and may entail conservative and surgical approaches. In this study, we performed a systematic review of reported cases to evaluate the clinical course and treatment options for these patients. A comprehensive systematic search of two databases was performed, and information on patient characteristics, symptomatology, and treatment was extracted from eligible articles. A total of 56 cases were included in our analyses. Forty patients were male, 16 were female, with an average age of 21.38 years at the time of diagnosis. Assumed etiology was previous trauma in 35 cases, previous cranial surgery in 17 patients, and birth trauma and epidural bleeding after the utilization of the Mayfield clamp in 1 case each. The origin remained unclear in two cases. The time between trauma or surgery and diagnostics ranged between one and a half weeks and 50 years, with a median of 4 years (SD 9.8 years). The symptoms were very heterogeneous, ranging from acute neurological deterioration to chronic symptoms. In 15 cases, patients were asymptomatic, and cranial imaging was performed as part of a new trauma or a screening for other disease. Forty-one patients received surgical treatment by craniotomy and hematoma evacuation, and 13 patients were treated conservatively. In two cases, the liquid hematoma portion was aspirated through a burr hole. The localization of calcified or ossified EDH was mainly supratentorial. Young male patients most commonly present with calcified or ossified EDH after trauma, according to the epidemiological trend of acute EDH. Clinical presentation varies from asymptomatic to severe neurological deficits and signs of increased intracranial pressure. There is no standardized treatment; decisions must be made on an individual basis.

Traumatic brain injuries (TBIs) may increase the risk for Alzheimer's disease (AD) and its neuropathological correlates, although the mechanisms of this relationship are unclear. The current study examined the synergistic effects of TBI and genetic risk for AD on β-amyloid (Aβ) levels among Vietnam War Veterans. We hypothesized that the combination of TBI and higher polygenic risk score (PRS) for AD would be associated with lower cerebrospinal fluid (CSF) Aβ_42/40. Data were obtained from the Department of Defense Alzheimer's Disease Neuroimaging Initiative. Participants included Vietnam War Veterans without dementia who identified as White non-Hispanic/Latino and had available demographic, clinical assessment, genetic, and CSF biomarker data. Lifetime TBI history was assessed using The Ohio State University TBI Identification Method. Participants were categorized into those with and without TBI. Among those with a prior TBI, injury severity was defined as either mild or moderate/severe. CSF Aβ_42/40 ratios were calculated. Genetic propensity for AD was assessed using PRSs. Hierarchical linear regression models examined the interactive effects of TBI and PRS for AD on Aβ_42/40. Exploratory analyses examined the interaction between TBI severity and PRS. The final sample included 88 male Vietnam War Veterans who identified as White non-Hispanic/Latino (M _age = 68.3 years), 49 of whom reported a prior TBI. There was a significant interaction between TBI and PRS, such that individuals with TBI and higher PRS for AD had lower Aβ_42/40 (B = -0.45, 95% CI: -0.86 to -0.05, p = 0.03). This relationship may be stronger with increasing TBI severity (p = 0.05). Overall, TBI was associated with lower Aβ_42/40, indicating greater amyloid deposition in the brain, in the context of greater polygenic risk for AD. These findings highlight who may be at increased risk for AD neuropathology following TBI.

Central autonomic and endocrine dysfunctions following traumatic brain injury (TBI) are believed to involve the hypothalamus; however, underlying mechanisms are unknown. Although chronic deficits might be caused by irreversible tissue damage, various neuroendocrine and autonomic symptoms are only observed transiently, suggesting they might result from a temporary alteration in the activity of hypothalamic neurons. We therefore examined if a mouse model of mild TBI could induce reversible autonomic phenotypes and cause acute changes in c-Fos expression within corresponding regions of the hypothalamus. Adult C57Bl/6 male mice were lightly anesthetized with isoflurane and subjected to TBI by lateral head impact using a Gothenburg impactor. Mice treated the same way, but without the head impact served as controls (shams). We monitored body weight and core body temperature by infrared thermography and performed immunohistochemistry against c-Fos in various regions of the hypothalamus. We determined that a projectile velocity of 9 m/s significantly delayed recovery from the anesthesia without inducing skull fractures and signs of discomfort disappeared within 3 h, as assessed by grimace scale. Compared with shams, TBI mice displayed a rapid decrease in core body temperature which resolved within 48 h. Daily body weight gain was also significantly lower in TBI mice on the day following injury but recovered thereafter. c-Fos analysis revealed a significantly higher density of c-Fos-positive cells in the paraventricular nucleus and a significantly lower density in the median preoptic nucleus and medial preoptic area. We conclude that mild TBI induced by a single lateral head impact in mice at 9 m/s produces acute and reversible symptoms associated with hypothalamic dysfunction accompanied by significant changes in c-Fos expression within relevant areas of the hypothalamus. These findings support the hypothesis that a temporary alteration of neuronal activity may underlie the expression of reversible central autonomic and neuroendocrine symptoms.

Traumatic spinal cord injury (SCI) causes debilitating motor and sensory deficits that impair functional performance, and physical rehabilitation is currently the only established therapeutic reality in the clinical setting. In this study, we aimed to assess the effect of exercise of different volume and timing of intervention on functional recovery and neuromuscular regeneration in a mouse model of compressive SCI. Mice were assigned to one of four groups: laminectomy only (SHAM); injured, without treadmill training (SCI); injured, treadmill trained for 10 min until day 56 postinjury (TMT1); and injured, treadmill trained for two 10-min cycles with a 10-min pause between them until day 28 postinjury followed by the TMT1 protocol until day 56 postinjury (TMT3). On day 7 postinjury, animals started an eight-week treadmill-training exercise protocol and were trained three times a week. TMT3 mice had the best results in terms of neuroregeneration, functional recovery, and muscle plasticity as measured by functional and morphometric parameters. In conclusion, the volume of exercise can modulate the quality of the regenerative response to injury, when started in the acute phase and adjusted according to the inflammatory window.

Enlarged perivascular spaces (EPVs) can be seen on magnetic resonance imaging (MRI) scans in various neurological diseases, including traumatic brain injury (TBI). EPVs have been associated with cognitive dysfunction and sleep disturbances; however, their clinical significance remains unclear. The goal of this study was to identify MRI burden of EPVs over time following TBI and to explore their relationship with postinjury outcomes. Individuals with TBI underwent postinjury data collection at Day 1 (blood), 2 weeks (blood, MRI, outcomes), and 6 months (blood, MRI, outcomes). EPV burden was assessed using T1 and FLAIR sequences on representative slices in the centrum semiovale, basal ganglia, and midbrain. Serum blood was assayed to measure concentrations of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Thirty-two participants with TBI were included (mean age 36.8 years, 78% male, 50% White). Total EPVs count did not significantly change from 2 weeks (23.5 [95% confidence interval or CI = 22.0-32.0]) to 6 months (26.0 [95% CI = 22.0-30.0], p = 0.16). For self-reported measures of sleep, there were no significant associations between EPVs count and Insomnia Severity Index (2 weeks: β = -0.004; 95% CI = -0.094, 0.086; 6 months: β = 0.002; 95% CI = -0.122, 0.125) or the subset of sleep questions on the Rivermead Post-Concussion Symptoms Questionnaire (2 weeks: β = -0.005; 95% CI = -0.049, 0.039; 6 months: β = -0.019; 95% CI = -0.079, 0.042). Functional outcome, determined by 6 months incomplete recovery (Glasgow Outcome Scale-Extended [GOS-E < 8]) versus complete recovery (GOS-E = 8), was significantly associated with a higher number of EPVs at 2 weeks (odds ratio = 0.94, 95% CI = 0.88-0.99). Spearman correlations showed no significant relationship between EPVs count and GFAP or NfL. This study used commonly acquired MRI sequences to quantify EPVs and investigated their utility as a potential imaging biomarker in TBI. Given the minimal change in EPVs over time, this period may not be long enough for potential recovery or may indicate that EPVs are structural findings that do not significantly change over time.

The purpose of this study was to identify the response of biomolecules and biomarkers that are associated with the central nervous system to aerobic exercise in human and pre-clinical models of concussion or mild traumatic brain injury (TBI), and to highlight the knowledge gaps in the literature. A systematic scoping review was conducted following a search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane Libraries performed on September 8, 2023 (from data base inception). The scoping review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Duplicates were removed and article screening was performed using an online systematic review management system. The search resulted in a total of 2,449 articles being identified, with 14 articles meeting the inclusion/exclusion criteria and having their data extracted. One study was conducted in humans, while the remainder of identified studies utilized murine models. The current literature is limited and evaluated many different biomolecules and biomarkers with brain-derived neurotrophic factor being the most researched. Further studies on this topic are needed to better understand the biomarker response to exercise after concussion and mild TBI, especially in the human population.