Sevoflurane alleviates early brain injury in rats with subarachnoid hemorrhage

Abstract

Objective To explore the protective mechanism of sevoflurane (Sev) on early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH). Methods Rats were randomly divided into sham operation group (sham group), model group , Sev low dose(Sev-L, 1.5%)and high dose (Sev-H, 3%) groups, Sev+Wnt/β-catenin signaling pathway specific inhibitor DKK1 group (Sev 3%+DKK1 5 μg/kg) with 18 rats in each. After 24 hours, the neurological function of rats was scored with the improved Garcia scale, the permeability of the blood-brain barrier was detected with Evans blue (EB), and the severity of SAH was evaluated with the SAH grading system; the brain tissue water content (BWC) was calculated; the neuronal apoptosis was detected with TUNEL immunofluorescence staining; the protein expression of Wnt3a, GSK-3β, p-GSK-3β, β-catenin, ZO-1, occludin and claudin-5, MMP-9, Bcl-2, Bax in brain tissue was detected with Western blot. Results Compared with the sham group, the neurological score, expression of Bcl-2, occludin, ZO-1, claudin-5, Wnt3a, and β-catenin in brain tissues in the model group reduced significantly (P＜0.05), the SAH score, EB exudation, cell apoptosis rate, expression of Bax, MMP-9, and p-GSK-3β/GSK-3β ratio in brain tissue increased significantly(P＜0.05); compared with model group, the neurological score, expression of Bcl-2, occludin, ZO-1, claudin-5, Wnt3a, and β-catenin in brain tissues in the Sev-L group and Sev-H group increased significantly(P＜0.05), the SAH score, EB exudation, cell apoptosis rate, expression of Bax, MMP-9, and p-GSK-3β/GSK-3β ratio in brain tissue reduced significantly (P＜0.05); DKK1 significantly weakened protective effect of Sev on EBI after SAH. Conclusions Sev may activate Wnt/β-catenin pathway, improve BBB, inhibit neuronal apoptosis and reduce EBI after SAH.

Keywords

• sevoflurane|subarachnoid hemorrhage|blood-brain barrier|neuronal apoptosis|wnt/β-catenin