脑卒中后胶质疤痕的形成至今没有有效的治疗方法，这一疤痕抑制了脑卒中后轴突生长和功能恢复。我们研究了由微胶质细胞调控的星形胶质细胞外泌体（AEV）是否能够调节胶质疤痕并改善脑卒中后的恢复。我们发现，梗死周围的胶质疤痕由反应性星形胶质细胞组成，这些细胞中有增殖的C3d和降低的S100A10表达在慢性脑卒中中。在培养的星形胶质细胞中，微胶质细胞调制培养基和P2Y1受体拮抗剂的处理通过抑制通气葡萄糖缺乏后的丝裂原活化蛋白激酶/核因子κβ（NF-κB）/肿瘤坏死因子α（TNF-α）/白细胞介素-1β（IL-1β）信号，分别增加和减少了S100A10和C3d表达的反应性星形胶质细胞面积。脑内给予富含miR-146a-5p的AEV通过下调NF-κB并抑制TNF-α的表达，将反应性星形胶质细胞转化为以S100A10为主导，促进大鼠中大脑动脉闭塞模型的功能恢复。调节脑卒中后胶质疤痕的神经炎症反应可能有利于轴突生长，为利用具有神经保护作用的AEV进行脑卒中恢复提供了基础。© 2023. 作者。

There are no effective treatments for post-stroke glial scar formation, which inhibits axonal outgrowth and functional recovery after stroke. We investigated whether astrocytic extracellular vesicles (AEVs) regulated by microglia modulate glial scars and improve stroke recovery. We found that peri-infarct glial scars comprised reactive astrocytes with proliferating C3d and decreased S100A10 expression in chronic stroke. In cultured astrocytes, microglia-conditioned media and treatment with P2Y1 receptor antagonists increased and reduced the area of S100A10- and C3d-expressing reactive astrocytes, respectively, by suppressing mitogen-activated protein kinase/nuclear factor-κβ (NF-κB)/tumor necrosis factor-α (TNF-α)/interleukin-1β signaling after oxygen-glucose deprivation. Intracerebral administrations of AEVs enriched miR-146a-5p, downregulated NF-κB, and suppressed TNF-α expressions, by transforming reactive astrocytes to those with S100A10 preponderance, causing functional recovery in rats subjected to middle cerebral artery occlusion. Modulating neuroinflammation in post-stroke glial scars could permit axonal outgrowth, thus providing a basis for stroke recovery with neuroprotective AEVs.© 2023. The Author(s).