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Protective effect of sevoflurane preconditioning on oxygen--glucose deprivation injury in rat hippocampal slices:the role of mitochondrial K_(ATP) channels

Wang Zhiping, Zhang Zhaohang, Zeng Yinming, Jiang Shan, Wang Shuqu, Wang Sheng

Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Jiangsu Province Institute of Anesthesiology.Xuzhou 221002，Jiangsu

Abstract

To investigate the neuroprotective effects of sevoflurane preconditioning and the role of mitochondrial K_(ATP) channels in oxygen-glucose deprivation injury in rats, we established oxygen-glucose deprivation injury model in rat hippocampal slices. The brain was rapidly removed, and the dissected hippocampus was sliced in cold artificial cerebrospinal fluid (ACSF) transversely to its longitudinal axis (400 #mu#m thick) with a Rotorslicer DTY-7700. Slices were placed on a nylon mesh in a recording chamber at 34℃ and humidified gas mixture (95% O_(2)/5% CO_(2)) was applied to the chamber at a flow rate of 1 L/min. After 2 hours of incubation, slices were randomly exposed to 2%, 4%, 6% sevoflurane or 6% sevoflurane combined with mitochondrial K_(ATP) channel blocker (5-hydroxydecanoic acid, 5-HD) under normal condition (95%O_(2)/5%CO_(2)) for 30 min. Fifteen minutes later, slices were exposed to 14-minute oxygen-glucose deprivation (OGD) followed by 1-hour reoxygenation，the changes of orthodromic population spike (OPS) at the end of reoxygenation were measured. The changes of ultrastructure of CA1 area 14-min OGD followed by 1-hour reoxygenation were detected with electron microscope. The results showed that sevoflurane preconditioning delayed the abolishing time of OPS (P<0.01) and increased significantly the recovery rate and the recovery amplitude of OPS compared with the OGD group. The recovery rate of OPS was 71.4% and 71.4% respectively in 4% and 6% sevoflurane preconditioning group (P<0.05), accordingly the recovery amplitude of OPS was (61.0±42.3)% and (78.7±21.1)% (P<0.01). The protective effect of 6% sevoflurane was blocked by 5-HD. Ultrastructural observation in the hippocampal CA1 region of the OGD group showed severe edema of the pyramidal cells, crimpled or ruptured nucleus membranes, aggregation of chromatin, and swelling of mitochondria,whereas in 4% and 6% sevoflurane groups these changes were less prominent. It is therefore suggested that sevoflurane preconditioning is capable to protect neurons from OGD injury in vitro and that the protective effect is related to the activation of mitochondrial K_(ATP) channels.

Key words: sevoflurane;cerebral injury;orthodromic population spike;mitochondrial ATP-sensitive potassium channels

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Citing This Article：

Wang Zhiping, Zhang Zhaohang, Zeng Yinming, Jiang Shan, Wang Shuqu, Wang Sheng. Protective effect of sevoflurane preconditioning on oxygen--glucose deprivation injury in rat hippocampal slices:the role of mitochondrial K_(ATP) channels. Acta Physiol Sin 2006; 58 (3): (in Chinese with English abstract).