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.

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Our current study has identified the impact of sevoflurane preconditioning on microglia/macrophage dynamics, including its migration, phagocytosis, and proliferation at early stage after brain ischemia and reperfusion. Sevoflurane might enhance microglia/macrophage activation and promote brain repair. These results could help to approach more relevant microglia/macrophage cell-based strategy for human stroke therapy.

Purpose of review Intraoperative hypotension (IOH) may render patients at a risk of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), and lead to postoperative neurological injury. On the basis of the literature in recent years, this review attempts to refine the definition of IOH and evaluate its impact on neurological outcomes. Recent findings Although both absolute and relative blood pressure (BP) thresholds, with or without a cumulative period, have been used in collective clinical studies, no definitive threshold of IOH has been established for neurological complications, including perioperative stroke, postoperative cognitive disorder and delirium. The CBF is jointly modulated by multiple pressure processes (i.e. cerebral pressure autoregulation) and nonpressure processes, including patient, surgical and anaesthesia-related confounding factors. The confounding factors and variability in cerebral pressure autoregulation might impede evaluating the effect of IOH on the neurological outcomes. Furthermore, the majority of the evidence presented in this review are cohort studies, which are weak in demonstrating a cause--effect relationship between IOH and neurological complications. The maintenance of target BP based on the monitoring of regional cerebral oxygen saturation (rScO2) or cerebral pressure autoregulation seems to be associated with the decreased incidence of postoperative neurological complications. Summary Despite the lack of a known threshold value, IOH is a modifiable risk factor targeted to improve neurological outcomes. Ideal BP management is recommended in order to maintain target BP based on the monitoring of rScO2 or cerebral pressure autoregulation.