Friedman J E, Haddad G G
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520.
Brain Res. 1994 Mar 28;641(1):57-64. doi: 10.1016/0006-8993(94)91815-5.
Anoxia is believed to cause nerve injury and death in part, by inducing sustained, elevated levels of intracellular Ca2+. The increased concentration of intracellular Ca2+ is capable, by itself, of inducing nerve injury and death, even without the added stress of anoxia. However, we have recently shown that an increased level of intracellular Ca2+ is not necessary for anoxia-induced CA1 nerve injury. Since we have observed that extracellular Na+ decreases during anoxia, we studied the role of extracellular Na+ in anoxia-induced nerve injury. Removal of extracellular Na+ and its replacement with the impermeant cation N-methyl-D-glucamine (NMDG+) completely protected freshly dissociated CA1 neurons during and after severe anoxia, for up to 90 min. Intracellular Ca2+ decreased during anoxia, recovering during reoxygenation. Propidium iodide was excluded from the neurons for as long as Na+ was absent. Addition of Na+ (by replacing NMDG+) following anoxia resulted in rapid bleb formation, swelling and intracellular Ca2+ rise. Removal of Na+ before the rupture of blebs caused either shrinkage or pinching off of blebs so that the neuron apparently returned to its previous undisturbed state.(ABSTRACT TRUNCATED AT 250 WORDS)
缺氧被认为部分是通过诱导细胞内钙离子持续升高而导致神经损伤和死亡。细胞内钙离子浓度的增加本身就能够诱导神经损伤和死亡，即使没有缺氧的额外压力。然而，我们最近发现，细胞内钙离子水平升高对于缺氧诱导的CA1神经损伤并非必要条件。由于我们观察到缺氧期间细胞外钠离子减少，因此我们研究了细胞外钠离子在缺氧诱导的神经损伤中的作用。去除细胞外钠离子并用非渗透性阳离子N-甲基-D-葡萄糖胺（NMDG+）替代，可在严重缺氧期间及之后长达90分钟内完全保护新鲜分离的CA1神经元。缺氧期间细胞内钙离子减少，复氧时恢复。只要没有钠离子，神经元就会排斥碘化丙啶。缺氧后添加钠离子（通过替换NMDG+）会导致迅速形成气泡、肿胀和细胞内钙离子升高。在气泡破裂前去除钠离子会导致气泡收缩或掐断，从而使神经元明显恢复到之前未受干扰的状态。（摘要截短于250字）
