Welsch M, Nuglisch J, Krieglstein J
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, FRG.
Stroke. 1990 Dec;21(12 Suppl):IV105-7.
In the present study, we investigated the protective effect of nimodipine against postischemic neuronal damage in the rat and considered the question of whether this histologic finding coincides with an improvement of cerebral circulation. Male Wistar rats were subjected to 10 minutes of forebrain ischemia by clamping both common carotid arteries and lowering blood pressure to 40 mm Hg. Histologic evaluation was performed 7 days after ischemia. Local cerebral blood flow was determined with the 14C-iodoantipyrine technique in anatomically defined areas of the brain, including hippocampus. Preischemic application of nimodipine (3.0 mg/kg p.o.) significantly reduced the percentage of damaged neurons in hippocampal CA1 subfield from 78 +/- 4% in controls to 59 +/- 6% in treated rats (mean +/- SEM; p less than 0.05, Mann-Whitney U test). After 10, 60, and 180 minutes of recirculation no differences in local cerebral blood flow between control and drug-treated animals were observed. Our results demonstrate that nimodipine reduces ischemia-induced neuronal damage in rat hippocampus. We did not consider increased cerebral blood flow in the hypoperfusion state in the applied experimental design since improvement of cerebral blood flow seems to bear little relation to the neuroprotective activity of nimodipine.
在本研究中，我们调查了尼莫地平对大鼠缺血后神经元损伤的保护作用，并探讨了这一组织学发现是否与脑循环改善相一致的问题。雄性Wistar大鼠通过夹闭双侧颈总动脉并将血压降至40 mmHg进行10分钟的前脑缺血。缺血7天后进行组织学评估。采用14C-碘代安替比林技术在包括海马体在内的大脑解剖学定义区域测定局部脑血流量。缺血前应用尼莫地平（3.0 mg/kg口服）可使海马CA1亚区受损神经元的百分比从对照组的78±4%显著降低至治疗组大鼠的59±6%（平均值±标准误；p<0.05，曼-惠特尼U检验）。再灌注10、60和180分钟后，未观察到对照组和药物治疗组动物之间局部脑血流量的差异。我们的结果表明，尼莫地平可减少大鼠海马体缺血诱导的神经元损伤。在应用的实验设计中，我们没有考虑低灌注状态下脑血流量的增加，因为脑血流量的改善似乎与尼莫地平的神经保护活性关系不大。
