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Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway.
J Neurol Sci. 2015 Jan 15; 348(1-2):216-25.JN

Abstract

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.

Authors+Show Affiliations

Department of Anesthesiology, Affiliated Xiangya Hospital of Central South University, Changsha 410078, Hunan Province, China.Department of Anesthesiology, Affiliated Xiangya Hospital of Central South University, Changsha 410078, Hunan Province, China.Department of Anesthesiology, Affiliated Xiangya Hospital of Central South University, Changsha 410078, Hunan Province, China.Department of Anesthesiology, Affiliated Xiangya Hospital of Central South University, Changsha 410078, Hunan Province, China. Electronic address: bennydoctor@live.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25555490

Citation

Ye, Zhi, et al. "Neuroprotection Induced By Sevoflurane-delayed Post-conditioning Is Attributable to Increased Phosphorylation of Mitochondrial GSK-3β Through the PI3K/Akt Survival Pathway." Journal of the Neurological Sciences, vol. 348, no. 1-2, 2015, pp. 216-25.
Ye Z, Xia P, Cheng ZG, et al. Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway. J Neurol Sci. 2015;348(1-2):216-25.
Ye, Z., Xia, P., Cheng, Z. G., & Guo, Q. (2015). Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway. Journal of the Neurological Sciences, 348(1-2), 216-25. https://doi.org/10.1016/j.jns.2014.12.011
Ye Z, et al. Neuroprotection Induced By Sevoflurane-delayed Post-conditioning Is Attributable to Increased Phosphorylation of Mitochondrial GSK-3β Through the PI3K/Akt Survival Pathway. J Neurol Sci. 2015 Jan 15;348(1-2):216-25. PubMed PMID: 25555490.
* Article titles in AMA citation format should be in sentence-case
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 -