Background and Purpose: We explored the effectiveness of dual blockade of calcium channels in preventing ischemic necrosis in a rat model of transient forebrain ischemia. Methods: To assess all the major brain regions, the entire brain was subseriallv sectioned and examined histologically 1 week after ischemia in 44 male Wistar rats. Brain temperature was monitored and controlled to avoid hypothermia or intergroup temperature differences at the time drugs were administered. All regimens were begun 20 minutes after the ischemia. Treated animals received either the L-type calcium channel blocker nimodipine (0.25 μg/min ×24-hour i.v. infusion), the noncompetitive N-raethylD-aspartate receptor antagonist MK-801 (dizocilpine; 5 mg/kg i.v.), or both regimens in combination. Results: In the neocortex (p<0.05) and striatum (p<0.05), only double-treated animals showed a statistically significant reduction in neuronal necrosis. Dual therapy eliminated neuronal necrosis in the caudate nucleus entirely. In the septaI (densely ischemic) hippocampus, protection was weak and inconsistent (0.012<p<0.788), but in the temporal (incompletely ischemic) hippocampus, the dualtreated group showed the most significant reduction (p<0.006). Conclusions: We conclude that the combination of nimodipine and MK-801, if begun 20 minutes after ischemia, may offer a neuroprotective effect against neuronal necrosis in transient forebrain ischemia and that protection is maximal in the major extrahippocampal brain regions.

Calcium channel blockers, Cerebral ischemia, Neuronal damage, Rats
Sprott School of Business

Rod, M, & Auer, R.N. (Roland N.). (1992). Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia. Stroke, 23(5), 725–732.