Isoflurane-induced neuronal apoptosis in developing hippocampal neurons

作     者：Hongliang Liu Tijun Dai Weitao Guo 

作者机构：Department of AnesthesiologyChongqing Cancer Institute/Cancer Hospital Department of PharmacologyXuzhou Medical College Department of Orthopedics Affiliated HospitalGuangdong Medical College 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2013年第8卷第9期

页      面：825-832页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China No.30471657 

主　　题：neural regeneration brain injury isoflurane P2X7 receptor inositol triphosphate receptor calciumhomeostasis disturbance neurodegenerative disease apoptosis developing brain hippocampus grants-supported paper photographs-containing paper neuroregeneration 

摘      要：We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca^2＋ Blockade of P2X7 receptors or removal of extracellular Ca^2＋ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca^2＋. Removal of extracellular Ca^2＋ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.