Prevention of Stroke and Brain Damage With Calcium Antagonists in Animals

Abstract

In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy.