✓ Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1,4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p < 0.001, p < 0.01, p < 0.05, respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p < 0.01, p < 0.01, p < 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the “penumbra” of the ischemic area.
Neuropathological Evaluation of Acrylamide- and 3,3’-Iminodipropionitrile-Induced Neurotoxicity in a Rat 28-Day Oral Toxicity Study-Collaborative Project for Standardization of Test Procedures and Evaluation of Neurotoxicity
