Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury via PI3K/Akt pathway.
Emerging evidence has demonstrated that postconditioning with sevoflurane provided neuroprotection. In this study, we investigated the neuroprotective effect of different concentrations of sevoflurane in rats with middle cerebral artery occlusion (MCAO). Furthermore, we tested the hypothesis that the neuroprotective effect of postconditioning with sevoflurane is associated with inhibition of apoptosis and mediated by activation of the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. Adult male Sprague-Dawley rats were subjected to MCAO for 90 min and then treated with sevoflurane at the beginning of reperfusion. The infarct volume, neurological deficit scores and brain edema were evaluated at 24 hours. Spatial learning and memory was examined by Morris water maze. Apoptosis and apoptosis-related proteins were studied by TUNEL, immunohistochemistry and western blot. The neuroprotective effect and the amount of p-Akt after sevoflurane administration with or without wortmannin were analyzed. Postconditioning with sevoflurane 1.0 minimum alveolar concentration (MAC) and 1.5 MAC significantly decreased neurological deficit scores, infarct volume and brain edema and markedly improved spatial learning and memory. Postconditioning also reduced apoptotic cells, upregulated Bcl-2 and downregulated P53 and Bax. Wortmannin abolished the neuroprotective effect and prevented the increasing of p-Akt. Our data suggest postconditioning with sevoflurane (1.0 MAC and 1.5 MAC) not only reduced infarct volume but also improved learning and memory. Our study further showed that this neuroprotective effect may be partly due to the activation of PI3K/Akt pathway and inhibiting neuronal apoptosis.
Wang
Jun-Kuan
JK
Department of Neurosurgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Yu
Li-Na
LN
Zhang
Feng-Jiang
FJ
Yang
Mei-Juan
MJ
Yu
Jing
J
Yan
Min
M
Chen
Gao
G
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D000077149:Sevoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt