TY - JOUR T1 - Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway. AU - Ye,Zhi, AU - Xia,Pingping, AU - Cheng,Zhi-gang, AU - Guo,Qulian, Y1 - 2014/12/18/ PY - 2014/06/27/received PY - 2014/11/16/revised PY - 2014/12/07/accepted PY - 2015/1/4/entrez PY - 2015/1/4/pubmed PY - 2016/5/27/medline KW - Apoptosis KW - Focal cerebral ischemia KW - Glycogen synthase kinase 3β (GSK-3β) KW - PI3K/Akt KW - Post-conditioning KW - Sevoflurane SP - 216 EP - 25 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 348 IS - 1-2 N2 - BACKGROUND AND PURPOSE: Post-conditioning with volatile anesthetics can create ischemic tolerance against cerebral ischemia-reperfusion injury. The present study was designed to determine whether delayed exposure to sevoflurane could induce ischemic tolerance and if this effect was dependent on increasing phosphorylated Akt-Ser473 and GSK-3β-Ser9 expression in the mitochondria, via a mechanism involving the PI3K/Akt pathway. METHODS: Adult male Sprague-Dawley rats were subjected to focal cerebral ischemia. Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 60 min, 15 min after reperfusion. Phosphorylated Akt-Ser473 and GSK-3β-Ser9 in the cytosol and mitochondria of the ischemic penumbra were evaluated 4, 12, 24, and 72 h after reperfusion. Neurological deficit score and activity of caspase-3 and -9 were evaluated 24 and 72 h after reperfusion. Apoptosis, as measured by TUNEL staining and cerebral infarct size,was determined 24h after reperfusion. RESULTS: Sevoflurane-delayed post-conditioning significantly increased levels of phosphorylated Akt-Ser473 and GSK-3β-Ser9 in the mitochondria and inhibited the activities of caspase-3 and -9, showing an improved neurological deficit score and a decreased infarct size. However, LY294002, a selective PI3K inhibitor, not only eliminated the neuroprotection of sevoflurane, as indicated by an increased infarct size and a larger number of TUNEL-positive cells, but also reversed the elevation of p-Akt and p-GSK-3β expression in the mitochondria induced by sevoflurane post-conditioning. CONCLUSIONS: Our data suggested that delayed application of sevoflurane after reperfusion provides neuroprotection by activating phosphorylated Akt-Ser473 and GSK-3β-Ser9 in the mitochondria via the PI3K/Akt pathway. SN - 1878-5883 UR - https://www.unboundmedicine.com/medline/citation/25555490/Neuroprotection_induced_by_sevoflurane_delayed_post_conditioning_is_attributable_to_increased_phosphorylation_of_mitochondrial_GSK_3β_through_the_PI3K/Akt_survival_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(14)00776-X DB - PRIME DP - Unbound Medicine ER -