Izumiyama K, Kogure K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Stroke. 1988 Aug;19(8):1003-7. doi: 10.1161/01.str.19.8.1003.
We used a gerbil model of cerebral ischemia to study the effects of ion channel blockers on neuronal death resulting from enhanced glutamate release and calcium ion influx. The common carotid arteries of gerbils were occluded for 5 minutes and injected intraperitoneally immediately after ischemia with an alkylene iminopropylene derivative (glutamate blocker) or a piperazinyl ethanol derivative (calcium blocker) given at high or low doses. Two vehicle groups received saline or 0.2% methyl cellulose solution. Seven days later, the gerbils were perfusion-fixed and their brains were processed for histologic study. The number of neurons per millimeter (neuronal density) of the CA1 region was calculated, and the neuronal density in each group was statistically compared using the Mann-Whitney U test. Compared with a control group not subjected to carotid ligation, neurons of the two vehicle groups and the low-dose calcium blocker group were almost nonexistent in the CA1 region. Neuronal densities of the glutamate blocker group and the high-dose calcium blocker group were similar and were found to be within normal limits by statistical analysis. Our study shows that detrimental membrane phenomena and the incidence of delayed neuronal death may be counteracted by the systemic administration of these ion channel blockers after ischemic insult.
我们使用沙土鼠脑缺血模型来研究离子通道阻滞剂对因谷氨酸释放增加和钙离子内流导致的神经元死亡的影响。将沙土鼠的双侧颈总动脉闭塞5分钟，缺血后立即腹腔注射高剂量或低剂量的亚烷基亚氨基丙基衍生物（谷氨酸阻滞剂）或哌嗪基乙醇衍生物（钙阻滞剂）。两个溶剂对照组分别接受生理盐水或0.2%甲基纤维素溶液。7天后，对沙土鼠进行灌注固定，并对其大脑进行组织学研究。计算CA1区每毫米的神经元数量（神经元密度），并使用Mann-Whitney U检验对每组的神经元密度进行统计学比较。与未进行颈动脉结扎的对照组相比，两个溶剂对照组和低剂量钙阻滞剂组的CA1区几乎不存在神经元。谷氨酸阻滞剂组和高剂量钙阻滞剂组的神经元密度相似，经统计学分析发现其在正常范围内。我们的研究表明，缺血性损伤后全身应用这些离子通道阻滞剂可能会抵消有害的膜现象和延迟性神经元死亡的发生率。
