Hira Kenichiro, Miyamoto Nobukazu, Inaba Toshiki, Xu Hai-Bin, Miyauchi Yoshifumi, Kijima Chikage, Urabe Takao, Hattori Nobutaka, Ueno Yuji
Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
J Cereb Blood Flow Metab. 2025 Jul 28:271678X251361247. doi: 10.1177/0271678X251361247.
Extracellular vesicles (EVs) derived from cells such as mesenchymal stem cells exert neurorestorative effects; however, the efficacy of circulating EVs for repairing injured brains and functional recovery after stroke remains unknown. This study shows that miR-451-5p in circulating EVs is crucial for stroke recovery, with its first therapeutic application in middle cerebral artery occlusion (MCAO) rats. Circulating EVs derived from MCAO rats in the chronic recovery phase were enriched in miR-451-5p, especially in CD9 EVs., increased S100A10 astrocytes and decreased C3d astrocytes in the peri-infarct area (PIA). They also increased axonemal phosphorylated high-molecular-weight neurofilaments and dendritic non-phosphorylated high-molecular-weight neurofilaments, reduced the infarct size, and enhanced functional recovery. EVs with miR-451-5p overexpression suppressed macrophage migration inhibitory factor in cultured neurons and cyclin D1 in cultured astrocytes after stroke. These findings indicate that miR-451-5p-enriched CD9 circulating EVs restored ischemic brain tissues, making them potential therapeutic targets for stroke.
源自间充质干细胞等细胞的细胞外囊泡（EVs）具有神经修复作用；然而，循环EVs对中风后受损大脑的修复及功能恢复的疗效仍不清楚。本研究表明，循环EVs中的miR-451-5p对中风恢复至关重要，首次在大脑中动脉闭塞（MCAO）大鼠中进行了治疗应用。慢性恢复期MCAO大鼠来源的循环EVs富含miR-451-5p，尤其是在CD9 EVs中，梗死周围区（PIA）的S100A10星形胶质细胞增加，C3d星形胶质细胞减少。它们还增加了轴丝磷酸化高分子量神经丝和树突非磷酸化高分子量神经丝，缩小了梗死面积，并促进了功能恢复。过表达miR-451-5p的EVs抑制了中风后培养神经元中的巨噬细胞迁移抑制因子和培养星形胶质细胞中的细胞周期蛋白D1。这些发现表明，富含miR-451-5p的CD9循环EVs可恢复缺血性脑组织，使其成为中风潜在的治疗靶点。
