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.
Highlights
Ischemic stroke, one of the most common disabling diseases, is mainly characterized by thromboembolic occlusion of the main artery supplying the brain
We found that miR-98 expression level was obviously downregulated in the serum of acute ischemic stroke patients compared with healthy controls and there were no significant differences between males and females (Fig. 1a, b)
In the ischemic stroke rat models induced by transient middle cerebral artery occlusion, the levels of miR-98 in the serum were decreased compared with sham group (Fig. 1c)
Summary
One of the most common disabling diseases, is mainly characterized by thromboembolic occlusion of the main artery supplying the brain. The ischemic brain induces highly dynamic alterations, interacting processes and limited remodeling of the neurovascular unit, involving dysfunction of endothelial cells, When neurons suffer threatens from ischemic stimuli, they activate self-preservation and release extracellular “help me” signals to adjacent cells and induce them to shift into beneficial phenotypes, to limit damage[5]. Some findings indicate that endangered or damaged neurons can release a repertoire of signaling molecules to instruct surrounding cells including microglia, control microglial function, and regulate microgliamediated phagocytosis and neuroprotection[6]. The signals involved in regulating the interactions between neurons and microglia remain unclear. EVs grasp our eyes as a flexible medium in cell-to-cell interaction[7,8,9].
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