Uematsu D, Araki N, Greenberg J H, Sladky J, Reivich M
Cerebrovascular Research Center, University of Pennsylvania, Philadelphia 19104.
Neurology. 1991 Jan;41(1):88-94. doi: 10.1212/wnl.41.1.88.
Calcium ion can enter ischemic neurons through both receptor-operated and voltage-sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal injury, we tried a combined treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist, nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3 hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood flow in the cat cortex using a newly developed fluorometric technique with indo-1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5 minutes into ischemia, was effective in reducing both Ca2+ entry and histologic damage and in enhancing recovery of the electroencephalogram following reperfusion. MK-801 alone was also effective, but to a lesser extent. These data suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a useful tool for protection against ischemic brain damage.
钙离子可通过受体操纵性和电压敏感性Ca2+通道进入缺血的神经元。为减轻这种Ca2+内流及Ca2+诱导的神经元损伤，我们在猫大脑中动脉闭塞（1小时）和再灌注（3小时）模型中尝试了用非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801和二氢吡啶类钙拮抗剂尼莫地平进行联合治疗。我们使用一种新开发的、以荧光细胞内Ca2+指示剂indo-1为基础的荧光测定技术，测量了猫皮质中胞质游离钙、烟酰胺腺嘌呤二核苷酸/还原型烟酰胺腺嘌呤二核苷酸氧化还原状态及血流的变化。在缺血5分钟时开始的联合治疗，在减少Ca2+内流和组织学损伤以及增强再灌注后脑电图恢复方面是有效的。单独使用MK-801也有效，但程度较小。这些数据表明，使用MK-801和尼莫地平双重阻断Ca2+内流可能是预防缺血性脑损伤的一种有用手段。
