Astrocytes are the most abundant glial cells in the central nervous system; they participate in crucial biological processes, maintain brain structure, and regulate nervous system function. Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins, peptides, nucleotides, and lipids secreted from their cellular sources. Increasing evidence shows that exosomes participate in a communication network in the nervous system, in which astrocyte-derived exosomes play important roles. In this review, we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system. We also discuss the potential research directions of the exosome-based communication network in the nervous system. The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain. New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

Inflammation is dominant in the pathogenesis of ischemic stroke (IS). Alpha‐ketoglutarate (AKG), according to previous studies, has demonstrated a variety of pharmacological effects such as antioxidation and inhibitive inflammation activities. However, whether AKG ameliorates cerebral ischemic injury, as well as the underlying molecular events, is still unclear. Therefore, the effect and underlying mechanisms of AKG on ischemic brain injury should be identified. The study established a cerebral ischemia‐reperfusion (I/R) model in mice as well as an oxygen‐glucose deprivation/reperfusion (OGD/R) model in SH‐SY5Y cells, respectively. It was observed that AKG markedly suppressed infarction volume and neuronal injuries and improved the neurological score in vivo. Moreover, AKG reduced the inflammatory response and lowered the expression of proinflammatory cytokines. In vitro, AKG treatment strongly inhibited OGD/R‐induced neuronal injury and the proinflammatory factors. It was also found that the increased SOD and GSH levels, as well as the lower ROS levels, showed that AKG reduced oxidative stress in OGD/R‐treated SY‐SY5Y cells. Mechanistically, AKG largely promoted IL‐10 expression in ischemic brain injury and OGD/R‐induced neuronal injury. Furthermore, IL‐10 silencing neutralized the protective effect of AKG on inflammation. Notably, it was discovered that AKG could upregulate IL‐10 expression by promoting the translocation of c‐Fos from the cytoplasm to the nucleus. The results indicated that AKG demonstrated neuroprotection on cerebral ischemia while inhibiting inflammation through c‐Fos/IL‐10/stat3 pathway.

Importance: Asymptomatic hemorrhagic infarction (HI) and subarachnoid hemorrhage (SAH) after endovascular treatment (EVT) for acute ischemic stroke are commonly considered low risk, but their long-term impact on functional outcomes is unclear.Objective: To determine whether asymptomatic HI and SAH are associated with worse 90-day functional recovery in patients with acute ischemic stroke treated with EVT.Design, Setting, and Participants: This is a secondary analysis of the DIRECT-MT randomized clinical trial, which compared intravenous thrombolysis prior to EVT with EVT alone. The multicenter study was conducted at tertiary hospitals in China between 2016 and 2019 with 90-day follow-up. Trial patients with asymptomatic HI, SAH, or no hemorrhage were included in the present analysis, which was performed in December 2024.Exposure: Asymptomatic HI and SAH detected on follow-up imaging.Main Outcomes and Measures: The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. Secondary analyses categorized mRS scores into thresholds of 0 to 1, 0 to 2, and 0 to 3, representing excellent, good, and favorable recovery, respectively.Results: A total of 490 patients were included (median [IQR] age, 70 [60-76] years; 210 [42.9%] female), with 133 (27.1%) in the asymptomatic HI and SAH group and 357 (72.9%) in the no hemorrhage group. After propensity score matching, the odds ratio of having a worse mRS scores at 90 days in the asymptomatic HI and SAH group compared with the no hemorrhage group was 2.59 (95% CI, 1.45-4.63; P = .001). For binary outcomes, asymptomatic HI and SAH were consistently associated with worse recovery across mRS score thresholds of 0 to 1 and 0 to 2 in all models.Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, asymptomatic HI and SAH were associated with worse 90-day functional outcomes in patients with acute ischemic stroke treated with EVT. These findings emphasize the need for close monitoring and tailored management strategies in patients with asymptomatic hemorrhagic events following thrombectomy.Trial Registration: ClinicalTrials.gov Identifier: NCT03469206