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Background: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. Methods: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. Results: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. Conclusions: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI. [ABSTRACT FROM AUTHOR]

Cranioplasty (CP) after decompressive craniectomy (DC) is routinely performed for reconstructive purposes and improves rehabilitation. However, the optimal timing of CP remains controversial. This study aimed to assess differences in clinical outcomes following different timings of CP in patients with traumatic brain injury. Patients with traumatic brain injury who underwent CP after DC in Zhongnan Hospital of Wuhan University from 1 January 2010 to 1 May 2017, and in Affiliated Hospital of Guizhou Medical University from 1 January 2015, to 1 May 2017, were retrospectively reviewed. According to the timing of CP, patients were divided into an 'early group' (3–6 months) and a 'late group' (6–12 months). The clinical characteristics of patients and postoperative complications occurred within 1-year follow-up were analysed. The neurological function was assessed with Barthel Index (BI). A total of 100 patients (58 cases in early group and 42 cases in late group) were included. The median interval between DC and CP was 135 days and 225 days in the early and late CP groups, respectively. The overall complication rate after CP was 16%, and no significant difference in complication rate was observed between the early and late CP groups (17.2% vs.14.3%, p = 0.69). The neurological function was improved in early CP group (pre-CP 85.77 ± 11.61 vs. post-CP 95.34 ± 9.02, p < 0.001, but not in late CP group (pre-CP 82.74 ± 22.82 vs. post-CP 88.93 ± 22.86, p = 0.22). In addition, a significantly higher proportion of patients in the early CP group showed neurological functional improvement in comparison with the late CP group (early vs. late: 74.1% vs. 57.1%, p = 0.04). Multivariate analysis further demonstrated that the timing of CP is an independent predictor for neurological outcomes (OR = 0.32, 95% CI 0.13–0.82, p = 0.02). Early CP (3–6 months) following posttraumatic DC was associated with better neurological outcomes than late CP (>6 months). [ABSTRACT FROM AUTHOR]

Introduction: Termed the "silent epidemic," traumatic brain injury (TBI) is one of the greatest global contributors not only to post-traumatic death but also to post-traumatic long-term disability. This systematic review and meta-analysis aims to specifically evaluate the prognostic value of features on initial imaging completed within 24 h of arrival in adult patients with TBI. Method: The authors followed the PRISMA 2020 checklist for systematic review and meta-analysis design and reporting. Comprehensive searches of the Medline and Embase databases were carried out. Two independent readers extracted the following demographic, clinical and imaging information using a predetermined data abstraction form. Statistics were performed using Revman 5.4.1 and R version 4.2.0. For pooled data in meta-analysis, forest plots for sensitivity and specificity were created to calculate the diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves were generated using a bivariate model, and diagnostic accuracy was determined using pooled sensitivity and specificity as well as the area under the receiver operator characteristic curve (AUC). Results: There were 10,733 patients over the 19 studies. Overall, most of the studies included had high levels of bias in multiple, particularly when it came to selection bias in patient sampling, bias in controlling for confounders, and reporting bias, such as in reporting missing data. Only subdural hematoma (SDH) and mortality in all TBI patients had both an AUC with 95% CI not crossing 0.5 and a DOR with 95% CI not crossing 1, at 0.593 (95% CI: 0.556–0.725) and 2.755 (95% CI: 1.474–5.148), respectively. Conclusion: In meta-analysis, only SDH with mortality in all TBI patients had a moderate but significant association. Given the small number of studies, additional research focused on initial imaging, particularly for imaging modalities other than NECT, is required in order to confirm the findings of our meta-analysis and to further evaluate the association of imaging findings and outcome. [ABSTRACT FROM AUTHOR]

Background: Photobiomodulation (PBM) using low-level light-emitting diodes (LEDs) can be rapidly applied to various neurological disorders safely and non-invasively. Materials and Methods: Forty-eight rats were involved in this study. The traumatic brain injury (TBI) model of rat was set up by a controlled cortical impact (CCI) injury. An 8-channel cortex electrode EEG was fixed to two hemispheres, and gamma oscillations were extracted according to each electrode. A 40 hz blue LED stimulation was set at four points of the frontal and parietal regions for 60 s each, six times per day for 1 week. Modified Neurologic Severity Scores (mNSS) were used to evaluate the level of neurological function. Results: In the right-side TBI model, the gamma oscillation decreased in electrodes Fp2, T4, C4, and O2; but significantly increased after 1 week of 40 hz Blue LED intervention. In the left-side TBI model, the gamma oscillation decreased in electrodes Fp1, T3, C3, and O1; and similarly increased after 1 week of 40 hz Blue LED intervention. Both left and right side TBI rats performed significantly better in mNSS after 40 hz Blue LED intervention. Conclusion: TBI causes the decrease of gamma oscillations on the injured side of the brain of rats. The 40 hz Blue LED therapy could relieve the gamma oscillation changes caused by TBI and improve the prognosis of TBI. Experimental grouping and process. [ABSTRACT FROM AUTHOR]