Sevoflurane Pretreatment On The Protective Effect And Mechanism Of Ischemic Brain Damage

Background and Purpose:The neuroprotection of volatile anesthetic preconditioning (APC) has been demonstrated in vivo and in vitro, yet the underlying mechanism is unclear. We therefore investigated whether attenuation of caspase3, apoptosis-inducing factor, Bcl-2, NF-kappa B along with downstream inflammatory factors, and p38 MAPK contributes to sevoflurane APC-induced neuroprotection.Methods:Male Sprague-Dawley rats were exposed for 30min/day on 4 consecutive days to ambient air,1.2% or 2.4% sevoflurane, which induces APC. Animals were subjected to filament occlusion of the middle cerebral artery for 60min at 24h after last sevoflurane pretreatment. Then rats were euthanized 0 to 24 hours later for detecting caspase-3, apoptosis inducing factor, Bcl-2, NF-kappa B, iNOS, COX-2, and p38 MAPK, then 3 days later for measuring neurologic deficit scores and infarct volume. In an additional experiment, rats were APC-treated as above with intracerebroventricμlar injection of lipopolysaccharide in place of occlusion of the middle cerebral artery.Results:Preconditioned with sevoflurane significantly decreased infarct volume and deficiency of neurologic function, suppressed caspase-3, apoptosis-inducing factor, inflammatory factors, NF-kappa B, and p38 MAPK, conversely, and increased level of antiapoptotic Bcl-2. Furthermore, sevoflurane APC restored the levels of NFκB, iNOS in an inflammatory model established by intracerebroventricular injection of lipopolysaccharide. Conclusion:The repetitive preconditioning of sevoflurane may provide neuroprotection against focal cerebral ischemia via attenuation of pro- or anti-apoptosis modulators and direct suppression of inflammatory factors.