Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM.

Numerous studies have elucidated the neuroprotective effect of 6-gingerol in central nervous system diseases. However, the potential role and mechanism of 6-gingerol on early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains poorly understood. Here, we report that 6-gingerol exerts a neuroprotective effect on SAH-induced EBI through the GBP2/PI3K/AKT pathway. A SAH rat model was established by injecting femoral artery blood into the cisterna magna. 6-gingerol or vehicle was injected intraperitoneally 1 hour post-SAH induction. We found that the neurological function score and brain edema of SAH rats were significantly improved after 6-gingerol treatment, as well as neuronal apoptosis was attenuated in SAH rats by Nissl staining assay and TUNEL assay. To further explore potential molecular mechanisms associated with 6-gingerol, RNA sequencing was implemented to investigate the differences in transcriptomes between SAH rats with and without 6-gingerol treatment; and found that the expression of guanylate-binding protein 2 (GBP2) evidently was suppressed with 6-gingerol treatment compared to vehicle group. In addition, dual immunofluorescence was also employed to investigate changes in neurons, astrocytes, and microglia after 6-gingerol treatment. The results showed that GBP2 was expressed in neurons but not astrocytes or microglia. Western blotting analysis results demonstrated that the PI3K/AKT pathway was activated in the SAH rats treated with 6-gingerol. Furthermore, recombinant GBP2 protein and LY294002 (PI3K inhibitor) treatment reversed the effects of 6-gingerol treatment in SAH rats. These results indicate that 6-gingerol suppressed the expression of GBP2 to activate the PI3K/AKT pathway, improve neurologic outcomes, reduce brain edema and neuronal apoptosis. In summary, our findings suggest that 6-gingerol could attenuate EBI post-SAH in rats, and 6-gingerol may serve as a novel candidate neuroprotective drug for SAH-induced EBI.

Background and aim: Most patients who present with a fourth ventricle tumor have concurrent hydrocephalus, and some demonstrate persistent hydrocephalus after tumor resection. There is still no consensus on the management of hydrocephalus in patients with fourth ventricle tumor after surgery. The purpose of this study was to identify the factors that predispose to postoperative hydrocephalus and the need for a postoperative cerebrospinal fluid (CSF) diversion procedure. Materials and methods: We performed a retrospective analysis of patients who underwent surgery of the fourth ventricle tumor between January 2013 and December 2018 at the Department of Neurosurgery in West China Hospital of Sichuan University. The characteristics of patients and the tumor location, tumor size, tumor histology, and preventive external ventricular drainage (EVD) that were potentially correlated with CSF circulation were evaluated in univariate and multivariate analysis. Results: A total of 121 patients were enrolled in our study; 16 (12.9%) patients underwent postoperative CSF drainage. Univariate analysis revealed that superior extension (p = 0.004), preoperative hydrocephalus (p<0.001), and subtotal resection (p<0.001) were significantly associated with postoperative hydrocephalus. Multivariate analysis revealed that superior extension (p = 0.013; OR = 44.761; 95% CI 2.235–896.310) and subtotal resection (p = 0.005; OR = 0.087; 95% CI 0.016–0.473) were independent risk factors for postoperative hydrocephalus after resection of fourth ventricle tumor. Conclusion: Superior tumor extension (into the aqueduct) and failed total resection of tumor were identified as independent risk factors for postoperative hydrocephalus in patients with fourth ventricle tumor.

Meningitis after microsurgery for vestibular schwannoma (VS) is a severe complication that results in high morbidity. However, few studies have focused on meningitis after VS surgery. The purpose of this study was to identify the risk factors for meningitis after VS surgery. We performed a retrospective analysis of all VS patients who underwent microsurgery and survived for at least 7 days after surgery, between 1 June 2015 and 30 November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM). We enrolled 410 patients, 27 of whom had POM. Through univariate analysis, the factors of hydrocephalus (p = 0.018), Koos grade IV (p = 0.04), operative duration > 3 hours (p = 0.03) and intraoperative bleeding volume ≥400 ml (p = 0. 02) were significantly correlated with POM. The multivariate analysis showed that Koos grade IV (p = 0.04; OR = 3.19; 95% CI 1.032–3.190), operation duration > 3 hours (p = 0.03; OR = 7.927; 95% CI 1.043–60.265), and intraoperative bleeding volume ≥ 400 ml (p = 0.02; OR = 2.551; 95% CI 1.112–5.850) were the independent influencing factors of POM. Koos grade IV, operation duration > 3 hours, and intraoperative blood loss ≥ 400 ml were identified as independent risk factors for POM after microsurgery for VS. POM also caused a prolonged hospital stay.

Background: The present study was performed to systematically quantify the association between egg consumption and stroke risk as inconsistent results have been produced. Methods: Three electronic databases (PubMed, Embase, and Cochrane Library), previous reviews, meta-analyses, and bibliographies of relevant articles were retrieved from prospective cohort studies published before July 1, 2020. The random-effects model was employed to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). A dose-response analysis was also performed when data were available. Results: Sixteen publications involving 24 prospective cohort studies were included in our final meta-analysis. No significant association between egg consumption and stroke risk was identified (RR = 0.92, 95% CI: 0.84–1.01) for the highest vs. the lowest quintiles of egg intake. Subgroup analysis indicated that geographic location significantly modified the effect of egg consumption on stroke risk. Higher egg consumption was attributed to a reduced probability of stroke in Asia (RR = 0.83, 95% CI: 0.73–0.94), but not in North America (RR = 0.95, 95% CI: 0.77–1.16) or Europe (RR = 1.02, 95% CI: 0.91–1.16). Dose-response analysis demonstrated a nearly J-shaped curve between egg consumption and risk of stroke. A decreased risk was observed for the intake of one to four eggs weekly and an increased risk for the intake of more than six eggs weekly. The results were significant at an intake of 10 eggs weekly. Conclusions: The evidence from this meta-analysis showed that a J-shaped association exists between egg consumption and stroke risk.