Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway

Abstract

In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1β, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.

Keywords: Apoptosis; Cerebral focal ischemia–reperfusion; PI3K; Sevoflurane preconditioning.