Journal of neurotrauma最新文献

Mild traumatic brain injury (mTBI) in children is a public health concern resulting in one of the main causes of pediatric emergency department (PED) visits. However, the acute care of mTBI patients remains challenging due to the limited use of specific and safe diagnostic tools. The objective of the study was to evaluate the performance of combined blood biomarkers in distinguishing between children with mTBI who had intracranial injuries (ICI) visible on CT scans and required hospitalization and those who did not. The aim was to safely discharge children with mTBI by ruling out the need for unnecessary CT scans and decreasing the length of stay in observation for symptoms monitoring in the PED. This was a prospective multicenter cohort study of children aged 0-16 years who presented to the PED within 24 h of sustaining mTBI. Blood was drawn at admission, and levels of IL6, neurofilament light (NfL) chain protein, N-terminal prohormone of brain natriuretic peptide (NTproBNP), glial fibrillary acidic protein (GFAP), IL10, S100 calcium-binding protein B, and heart fatty acid binding protein were analyzed. Biomarker performances to identify patients without ICIs were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. Patients were dichotomized into two groups: (1) with ICI on CT (=CT+) and (2) without ICI on CT or kept in observation without CT (=CT- and Obs.). All CT scans were reviewed by the same pediatric radiologist, following Pediatric Emergency Care Applied Research Network criteria to identify the presence of ICI. Biomarker age correlation was assessed in a healthy group of children aged 0-16 years. 419 children with mTBI and 99 healthy children were enrolled. Twenty-three percent (n = 97/419) of children underwent CT scan examination, while the other (n = 322/419) were kept in observation at the PED. Nineteen percent (n = 18/97) of the children who underwent a CT scan had ICI (=CT+), corresponding to four percent of all mTBI included patients. All the single and duplex combinations of blood-biomarkers were tested for their capacity to safely rule out ICI. IL6 was present in the three best combinations, reaching 100% sensitivity (SE) and with the highest associated specificity (SP). IL6 + NfL yielded 61% SP, followed by IL6 + NTproBNP with 60% SP, and IL6 + GFAP with 57% SP. Neither IL6 nor NTproBNP was found to be age correlated. IL6 in combination with either NfL, NTproBNP, or GFAP could safely rule out 61% of children without ICI (corresponding to 33/79 unnecessary CT scans and 212/322 observation stays at PED). Blood panels incorporating IL6 show promise as decision-making tools for the acute management of children with mTBI. However, further external studies are required to validate these findings.

High-quality evidence to guide the practice of acute cranial surgery across age groups in traumatic brain injury (TBI) remains sparse. Current surgical guidelines generally do not consider age in their recommendations. The aim of the study is to evaluate acute cranial surgery rates and center treatment differences across age in TBI. Data were extracted from the prospective observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The CENTER-TBI study included patients with TBI between 2014 and 2017 from 65 level 1 trauma centers across Europe and Israel. Data from all 27,358 patients with TBI enrolled in the CENTER-TBI core study (n = 4509) and registry (n = 22,849) were considered. Eight patients with missing age were excluded, leading to a final analytic sample of 27,350 (core study n = 4504, registry n = 22,846). Variations in probability, defined as case-mix adjusted proportions, of acute surgical treatment of intracranial mass effect (primary decompressive craniectomy or craniotomy), performed within 24 h of initial injury, were expressed using median odds ratios (MORs). Adjusted odds ratios (aORs) were calculated using random-effects linear regression to assess the association between age and the probability of acute cranial surgery for acute subdural hematoma, epidural hematoma, or intracerebral hemorrhage/contusions. MORs and aORs were reported with 95% confidence interval (CI). The odds of acute surgery decreased with older age (aOR = 0.93, 95% CI: 0.92-0.95, per each interquartile range increase of 37 years [y]). Variations in center-specific surgery rates increased with age (15-24 y: MOR = 1.4; 25-44 y: MOR = 1.5; 45-64 y: MOR = 1.6; 65-79 y: MOR = 1.8; ≥80 y: MOR = 3.3), except for patients aged <15 y (MOR = 2.9). Older patients with TBI were less likely to receive acute cranial evacuation surgery, independent from other (comorbidity) factors. Higher age was associated with more surgical treatment variation between centers. Neurosurgery for TBI can be improved by age-personalized treatment algorithms.

Macrophage-mediated efferocytosis is crucial for hematoma absorption and inflammation resolution in intracranial hemorrhages. We previously demonstrated that atorvastatin (ATO) expedites the absorption of subdural hematoma (SDH); however, the extent to which this therapeutic effect is associated with ATO-mediated modulation of macrophage efferocytosis remains unclear. In this study, we established a rat model of SDH through autologous blood transfusion into the subdural space. We used primary bone marrow-derived macrophages (BMDMs) to investigate the roles of heme and ATO. The results of enzyme-linked immunosorbent assay and flow cytometry demonstrated that, in addition to its proinflammatory effect, heme also inhibits macrophage efferocytosis. However, ATO reversed this inhibition of efferocytosis in both in vivo and in vitro experiments. Transcriptomic analysis of BMDMs revealed that ATO promotes Krüppel-like factor 4 (KLF4) expression and is mainly enriched in phagocytosis and lysosome-related pathways. Finally, ATO restored the heme-induced reduction in the macrophage phagocytic rate and impairment of lysosomal function. However, KLF4 knockout abolished the beneficial effects of ATO. In conclusion, this study demonstrated that ATO ameliorates heme-inhibited efferocytosis via KLF4, thereby promoting hematoma absorption. We demonstrated a novel mechanism of ATO in the treatment of SDH, providing a new therapeutic prospect for patients (IRB2022-YX-007-01).

Repetitive head impacts (RHIs) in soccer have been associated with long-term risk for neurodegenerative disease. The pathophysiology is largely unknown. This study aims to investigate alterations in cerebral blood flow (CBF) in athletes exposed to RHI compared with athlete controls (CTL). Given that females are known to exhibit higher CBF than males, we also explore sex-specific differences. Finally, we investigate the relationship between CBF and neuropsychological functioning and RHI measures. This study includes 82 amateur athletes (mean age 22.8 ± 1.6 years; 48.9% female). Participants underwent 3T magnetic resonance imaging and completed neuropsychological testing, including questionnaires on stress, resilience, and sleep quality, and computerized assessment of executive function, memory, and processing speed. CBF was assessed using MR pulsed arterial spin labeling. Analysis of covariance was applied to assess the effect of RHI exposure and sex on CBF. Associations between CBF and neuropsychological functioning were analyzed using linear regression models. The analysis was conducted hierarchically, beginning with global gray matter CBF (level 1), followed by cortical and deep gray matter (level 2), and finally brain lobes (level 3). Correction for multiple comparisons was applied at each hierarchical level using false discovery rate, with a significance threshold set at p < 0.05 after correction. We found higher CBF in athletes with RHI exposure (RHI group) compared with athletes with <5 years of exposure to RHI (CTL group; Δ 95% confidence interval [95% CI] = 3.9 [0.5, 7.3] mL/100g/min, p = 0.027). Female athletes with RHI exposure exhibited higher CBF in the global gray matter compared with female CTL (Δ[95% CI] = 6.6 [1.6, 11.5] mL/100g/min, p = 0.013). Among males, individuals with RHI exposure demonstrated higher CBF in the occipital lobe compared with male CTL (Δ[95% CI] = 4.9 [0.3, 9.5] mL/100g/min, p = 0.047). There were no statistically significant associations between CBF and neuropsychological functioning. In the RHI group, years of soccer play were positively associated with whole-brain CBF. Results from this study suggest an association between RHI exposure and higher CBF, a measure of brain activity. Furthermore, we report sex-specific patterns of higher CBF in individuals exposed to RHI, with more widespread elevated CBF in women and more localized higher CBF in men. While these findings highlight the importance of investigating sex-specific effects, there were no associations between CBF and neuropsychological functioning. Future studies are warranted to determine the clinical relevance of the observed sex-specific effects to RHI.

Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory sequelae that start immediately post-injury, remain for weeks, and can develop into long-term systemic inflammation. Studies have shown that TBI influences multiple physiological systems, including the gastrointestinal tract, through bidirectional communication modulated, in part, by the gut microbiome. Brainstem functioning post-TBI, as measured by acoustic startle sensorimotor processing, might play a role in this feedback loop. The current study investigated pre- to post-TBI (lateral fluid percussion injury model) changes in microbial communities and acoustic startle response in male and female rats. That is, the influence of mTBI on gut microbiome and sensorimotor processing was explored to examine: 1) overall and sex-specific differences in the gut microbiome and taxa in response to mTBI; 2) overall and sex-specific differences in sensorimotor processing following mTBI; and 3) associations between the gut microbiome and sensorimotor processing. Results showed mTBI had a limited effect on microbial diversity overall, and the same was observed in males and females independently. Yet, mTBI was associated with differences in 13 genus-level taxa. Further evaluation highlighted that 11 of the 13 genus-level taxa were sex-specific, with several being known to have short-chain fatty acid-producing capabilities. Alterations in sensorimotor processing were identified following mTBI; however, no sex-specific differences were evident. In addition, no associations were observed between sensorimotor processing and the gut microbiome. This study contributes longitudinal and sex-specific findings to the growing body of research examining the diverse effects of mTBI on the brain and gut microbial communities.