Exercise preconditioning increases circulating exosome miR-124 expression and alleviates apoptosis in rats with cerebral ischemia-reperfusion injury

Abstract

Objectives: Exercise as a non-pharmacological intervention can exert beneficial effects directly through exosomes crossing the blood-brain barrier and reduce apoptosis after cerebral ischaemia/reperfusion injury (CI/RI). miRNA-124 (miR-124) is present in exosomes and plays an important role in regulating cerebral neurological activity; however, the mechanism of the relationship between exercise and the activity of exosomes and apoptosis after CI/RI remains unclear. Therefore, the present study investigated the effects of exercise preconditioning on CI/RI from the perspective of exosomal miR-124 and apoptosis.

Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by blocking the middle cerebral artery, and a motorized running wheel was chosen as the method of exercise preconditioning for rats, the morphology, particle concentration and particle size distribution of the exosome samples were identified at the 6 h, 12 h, and 24 h time points. RT-PCR, western blotting, immunohistochemistry, TUNEL staining, TTC staining and mNSS scores were used to investigate the effects of exercise preconditioning on apoptosis in MCAO/R rats.

Results: The results showed exercise reduced neurological dysfunction and infarct size, increased the content of plasma exocrine miR-124 at 24 h, which inhibited the expression of STAT3, increased the expression of the anti-apoptotic BCL-2, and decreased the expression of the pro-apoptotic BAX, thereby reducing apoptosis.

Conclusions: Our findings indicated that exercise preconditioning can enhance the anti-apoptotic capacity of tissues in the rat ischemic penumbra and reduce apoptosis after CI/RI via the exosomal miR-124, STAT3, BCL-2/BAX pathway.

Keywords: Apoptosis; Cerebral ischemia–reperfusion; Exercise preconditioning; miR-124.