Giffard R G, Monyer H, Christine C W, Choi D W
Department of Anesthesia, Stanford University Medical center, CA 94305.
Brain Res. 1990 Jan 8;506(2):339-42. doi: 10.1016/0006-8993(90)91276-m.
The acidosis which accompanies cerebral ischemia in vivo has been thought to contribute to subsequent neuronal injury. However, recent electrophysiological recordings from hippocampal neurons suggest that H+ can attenuate N-methyl-D-aspartate (NMDA) receptor-mediated cation influx, likely a key event in the pathogenesis of ischemic neuronal injury. Here we report that moderate extracellular acidosis (pH 6.5) markedly reduced the inward whole cell current induced by NMDA on cultured cortical neurons; at pH 6.1, kainate-induced current was additionally reduced. Furthermore, such acidosis reduced the cortical neuronal injury caused by toxic glutamate exposure, as well as the neuronal degeneration and accumulation of 45Ca2+ induced by combined oxygen and glucose deprivation. These findings raise the possibility that moderate acidosis may decrease cortical neuronal vulnerability to ischemic damage.
体内脑缺血时伴随的酸中毒被认为会导致随后的神经元损伤。然而，最近来自海马神经元的电生理记录表明，H⁺ 可减弱 N - 甲基 - D - 天冬氨酸（NMDA）受体介导的阳离子内流，这可能是缺血性神经元损伤发病机制中的一个关键事件。在此我们报告，适度的细胞外酸中毒（pH 6.5）显著降低了NMDA对培养的皮质神经元诱导的内向全细胞电流；在pH 6.1时，海人酸诱导的电流进一步降低。此外，这种酸中毒减少了由毒性谷氨酸暴露引起的皮质神经元损伤，以及由联合缺氧和无糖培养诱导的神经元变性和45Ca²⁺ 的积累。这些发现提出了适度酸中毒可能降低皮质神经元对缺血性损伤易感性的可能性。
