Lazarewicz J W, Pluta R, Puka M, Salinska E
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Stroke. 1990 Dec;21(12 Suppl):IV108-10.
The purpose of this study was to verify the possible involvement of nimodipine-sensitive calcium channels in ischemic Ca2+ influx to hippocampal neurons to assess their role in nimodipine neuroprotection. We induced 15-minute global cerebral ischemia in pentobarbital-anesthetized and relaxed rabbits, which had been implanted with a transhippocampal dialysis probe, by intrathoracic artery occlusion combined with hypotension. A part from electroencephalographic and morphologic observations, changes in the extracellular concentrations of calcium, amino acids, and blood-brain barrier permeability to fluorescein were detected by microdialysis of the hippocampus. Nimodipine was applied either intravenously or locally to the hippocampus before, during, and after ischemia. Application of nimodipine locally or systemically, which had no effect on extracellular amino acids, enhanced recovery and normalization of the electroencephalographic activity and protected hippocampal neurons from early morphologic changes. Intravenous nimodipine reduced the ischemia-evoked drop of extracellular Ca2+ and completely prevented postischemic leakage of the blood-brain barrier, whereas local nimodipine infusion did not modify these ischemic disturbances. Our results suggest that nimodipine-sensitive Ca2+ channels play a minor role in the ischemic calcium influx to hippocampal neurons. Nimodipine, apart from a potent vasotropic action, may also directly protect brain neurons by intracellular calcium antagonism rather than by inhibition of calcium influx.
本研究的目的是验证尼莫地平敏感的钙通道是否可能参与缺血时海马神经元的Ca2+内流，以评估它们在尼莫地平神经保护作用中的作用。我们通过胸内动脉闭塞联合低血压，在植入经海马透析探针的戊巴比妥麻醉且肌肉松弛的家兔中诱导15分钟的全脑缺血。除了脑电图和形态学观察外，通过海马微透析检测细胞外钙、氨基酸浓度的变化以及血脑屏障对荧光素的通透性。在缺血前、缺血期间和缺血后，将尼莫地平静脉注射或局部应用于海马。局部或全身应用尼莫地平对细胞外氨基酸无影响，但增强了脑电图活动的恢复和正常化，并保护海马神经元免受早期形态学变化的影响。静脉注射尼莫地平减少了缺血引起的细胞外Ca2+下降，并完全防止了缺血后血脑屏障的渗漏，而局部注入尼莫地平并未改变这些缺血性干扰。我们的结果表明，尼莫地平敏感的Ca2+通道在缺血时海马神经元的钙内流中起次要作用。尼莫地平除了具有强大的向血管作用外，还可能通过细胞内钙拮抗作用而非抑制钙内流直接保护脑神经元。
