NEUROPROTECTIVE EFFECTS OF GLUTAMATE ANTAGONISTS AND EXTRACELLULAR ACIDITY
NEUROPROTECTIVE EFFECTS OF GLUTAMATE ANTAGONISTS AND EXTRACELLULAR ACIDITY
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DOI：
10.1126/science.8389056
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发表时间：
1993-06-04
期刊：
影响因子：
56.9
通讯作者：
CHOI, DW
中科院分区：
文献类型：
--
作者：
KAKU, DA;GIFFARD, RG;CHOI, DW
谷氨酸拮抗剂在体内和体外均可保护神经元免受缺氧损伤，但尚未在体内缺氧缺血典型的酸性条件下进行体外研究。与谷氨酸受体拮抗作用一致，细胞外酸度减少了缺氧和葡萄糖的小鼠皮质培养物中的神经元死亡。在这些酸性条件下，N-甲基-D-天冬氨酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯-红藻氨酸拮抗剂进一步减少了神经元死亡，使得一些神经元几乎与星形胶质细胞一样耐受长时间的缺氧和葡萄糖剥夺。这种组合诱导的神经保护作用超过了单独的谷氨酸拮抗剂诱导的神经保护作用，表明细胞外酸度除了减弱离子型谷氨酸受体激活之外还具有有益作用。
Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.