Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.
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.
Uematsu
D
D
Department of Neurology, University of Pennsylvania, Philadelphia 19104-6063.
Greenberg
J H
JH
Hickey
W F
WF
Reivich
M
M
D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003250:Constriction; D003600:Cytosol / Q000378:metabolism; D004569:Electroencephalography; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009243:NAD / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use
D009243:NAD; D009553:Nimodipine; D002118:Calcium