Ischemic neuroprotection afforded by sevoflurane preconditioning has been previously demonstrated, yet the underlying mechanism is poorly understood and likely affects a wide range of cellular activities. Several individual microRNAs have been implicated in both the pathogenesis of cerebral ischemia and cellular survival, and are capable of affecting a range of target mRNA. Conceivably, sevoflurane preconditioning may lead to alterations in ischemia-induced microRNA expression that may subsequently exert neuroprotective effects. We first examined the microRNA expression profile following transient cerebral ischemia in rats and the impact of sevoflurane preconditioning. Microarray analysis revealed that 3 microRNAs were up-regulated (>2.0 fold) and 9 were down-regulated (< 0.5 fold) following middle cerebral artery occlusion (MCAO) compared to sham controls. In particular, miR-15b was expressed at significantly high levels after MCAO. Preconditioning with sevoflurane significantly attenuated the upregulation of miR-15b at 72h after reperfusion. Bcl-2, an anti-apoptotic gene involved in the pathogenesis of cerebral ischemia, has been identified as a direct target of miR-15b. Consistent with the observed downregulation of miR-15b in sevoflurane-preconditioned brain, post-ischemic Bcl-2 expression was significantly increased by sevoflurane preconditioning. We identified the 3’-UTR of Bcl-2 as the target for miR-15b. Molecular inhibition of miR-15b was capable of mimicking the neuroprotective effect of sevoflurane preconditioning, suggesting that the suppression of miR-15b due to sevoflurane contributes to its ischemic neuroprotection. Thus, sevoflurane preconditioning may exert its anti-apoptotic effects by reducing the elevated expression of miR-15b following ischemic injury, allowing its target proteins, including Bcl-2, to be translated and expressed at the protein level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.