Cell Death Dis. 2021 Jan 6;12(1):23.doi: 10.1038/s41419-020-03310-2.

Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke

Jin Yang  1 Lu-Lu Cao  1   2 Xi-Peng Wang  1 Wei Guo  1 Ruo-Bing Guo  1 Yu-Qin Sun  1 Teng-Fei Xue  1 Zhen-Yu Cai  1 Juan Ji  1 Hong Cheng  3 Xiu-Lan Sun  4   5 Affiliations

Free PMC article

Abstract

Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.

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