Background
Cerebral ischemic stroke is a refractory disease which seriously endangers human health. Remote ischemic perconditioning (RiPerC) by which the sublethal ischemic stimulus is administered during the ischemic event is beneficial after an acute stroke. However, the regulatory mechanism of RiPerC that relieves cerebral ischemic injury is still not completely clear.
Conclusion
Our finding indicated that RiPerC inhibited the MCAO-induced expression of PIK3IP1 through upregulated miR-98, thereby reducing the apoptosis induced by PIK3IP1 through the PI3K/AKT signaling pathway, thus reducing the cerebral ischemia-reperfusion injury.
Methods
In the present study, we investigated the regulatory mechanism of RiPerC in a rat model of ischemia induced by the middle cerebral artery occlusion (MCAO). Forty-eight adult male Sprague-Dawley (SD) rats were injected intracerebroventricularly with miR-98 agomir, miR-98 antagomir, or their negative controls (agomir-NC, antagomir-NC) 2 h before MCAO or MCAO+RiPerC followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. The expression of miR-98, PIK3IP1, and tight junction proteins in rat hippocampus and cerebral cortex tissues was detected by quantitative polymerase chain reaction (qPCR) and Western blot (WB). Enzyme-linked immunosorbent assay (ELISA) was used to assess the IL-1β, IL-6, and TNF-α levels in the rat serum.
Results
The results showed that in MCAO group, the expression of PIK3IP1 was upregulated, but decreased after RiPerC treatment. Then, we found that PIK3IP1 was a potential target of miR-98. Treatment with miR-98 agomir decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control rats. But treating with miR-98 antagomir in RiPerC group, the protective effect on cerebral ischemia injury was canceled.