Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.
Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.
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DOI：
10.1161/01.str.20.11.1531
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发表时间：
1989-11
期刊：
影响因子：
8.3
通讯作者：
D. Uematsu;J. Greenberg;W. Hickey;M. Reivich
中科院分区：
文献类型：
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作者：
D. Uematsu;J. Greenberg;W. Hickey;M. Reivich
为阐明尼莫地平治疗缺血性脑卒中的作用机制，我们研究了尼莫地平（一种二氢吡啶类钙拮抗剂）对14只猫局灶性脑缺血再灌注后胞浆游离钙、皮质血流量和组织学变化的影响。使用indo-1，荧光细胞内Ca 2+指示剂，我们同时测量的Ca 2+信号比（400：506 nm），减少烟酰胺腺嘌呤二核苷酸荧光（464 nm），和反射率（340 nm）在紫外线激发（340 nm）直接从猫皮质在体内的变化。在仅用溶剂处理的6只猫中，钙信号比从大脑中动脉闭塞后5分钟至再灌注后30分钟增加。尼莫地平，这是通过静脉输注在8只猫开始5分钟后闭塞的细胞内游离钙的升高显着衰减。尼莫地平在缺血时对皮质血流量没有影响，但在再灌注后诱导了高灌注状态。尼莫地平没有修改线粒体氧化还原状态的变化。尼莫地平被证明对再灌注后脑电图的恢复以及局灶性组织学损伤的程度有有益的影响。我们的研究结果表明，尼莫地平，在局灶性缺血的早期阶段，可以有利地修改中风的结果，通过减少在缺血和再灌注期间的Ca 2+进入。
To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.