Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen-glucose-deprivation in organotypic hippocampal slice cultures
Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen-glucose-deprivation in organotypic hippocampal slice cultures
复制标题
DOI：
10.1016/j.neuroscience.2004.06.074
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Reiser, G
中科院分区：
文献类型：
--
作者：
Martinez-Sánchez, M;Striggow, F;Reiser, G
细胞内ATP供应和离子稳态决定缺血性中风后神经元的存活和变性。本研究提供了一个系统的调查，在器官型海马脑片培养的影响，实验性缺血，诱导的氧-葡萄糖剥夺（OGD）。控制细胞内Na+和Ca2+浓度（[Na +]和[Ca2 +]（i））的途径及其抑制与延迟的细胞死亡或保护相关。OGD可引起锥体神经元胞体ATP水平明显降低，[Ca~（2+）]（i）和[Na~+]（i）一过性升高。ATP水平、[Na +]（i）和[Ca~（2+）]（i）在重新引入氧和葡萄糖后迅速恢复。药理学分析表明，OGD引起的神经细胞索马胞体[Ca~（2+）]（i）升高是由N-甲基-D-天冬氨酸（NMDA）-谷氨酸受体和Na~+/Ca~（2+）交换体激活引起的，而OGD引起的[Na~+]（i）异常升高则是由电压依赖性Na~+通道的Na~+内流引起的。在海马切片中，OGD后24小时发生的细胞变性通过凋亡和非凋亡细胞死亡选择性地影响锥体细胞群。OGD诱导的细胞损失介导的离子型谷氨酸受体的激活，电压依赖性Na+通道，质膜和线粒体Na +/Ca2+交换。因此，我们表明，通过阻断NMDA受体和质膜Na +/Ca 2+交换剂诱导的神经保护是通过减少Ca 2+进入神经元索马介导的，而通过阻断AMPA/红藻氨酸受体和线粒体Na +/Ca 2+交换剂诱导的神经保护可能是由于树突水平的Na+进入减少。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Intracellular ATP supply and ion homeostasis determine neuronal survival and degeneration after ischemic stroke. The present study provides a systematic investigation in organotypic hippocampal slice cultures of the influence of experimental ischemia, induced by oxygen-glucose-deprivation (OGD). The pathways controlling intracellular Na+ and Ca2+ concentration ([Na+], and [Ca2+](i)) and their inhibition were correlated with delayed cell death or protection. OGD induced a marked decrease in the ATP level and a transient elevation of [Ca2+](i) and [Na+](i) in cell soma of pyramidal neurons. ATP level, [Na+](i) and [Ca2+](i) rapidly recovered after reintroduction of oxygen and glucose. Pharmacological analysis showed that the OGD-induced [Ca2+](i) elevation in neuronal cell soma resulted from activation of both N-methyl-D-aspartate (NMDA)-glutamate receptors and Na+/Ca2+ exchangers, while the abnormal [Na+](i) elevation during OGD was due to Na+ influx through voltage-dependent Na+ channels. In hippocampal slices, cellular degeneration occurring 24 h after OGD, selectively affected the pyramidal cell population through apoptotic and non-apoptotic cell death. OGD-induced cell loss was mediated by activation of ionotropic glutamate receptors, voltage-dependent Na+ channels, and both plasma membrane and mitochondrial Na+/Ca2+ exchangers. Thus, we show that neuroprotection induced by blockade of NMDA receptors and plasma membrane Na+/Ca2+ exchangers is mediated by reduction of Ca2+ entry into neuronal soma, whereas neuroprotection induced by blockade of AMPA/kainate receptors and mitochondrial Na+/Ca2+ exchangers might result from reduced Na+ entry at dendrites level. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.