Nimodipine binding in focal cerebral ischemia

We investigated the binding properties of the voltage-sensitive calcium channel antagonist nimodipine in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 250 g underwent occlusion of both the proximal middle cerebral artery and the ipsilateral common carotid artery. 3H-nimodipine (130 Ci/mmol) was infused intravenously and circulated for 30 minutes before the rats were killed at 5 minutes, 4, 24, and 48 hours after occlusion. The brains were removed and examined by autoradiography. We observed a focal increase of nimodipine binding in severely ischemic regions at 5 minutes after occlusion, which also appeared in regions with presumed penumbral blood flow levels at 4 hours after occlusion. We hypothesize that nimodipine binds to activated calcium channels in ischemic tissue. This increased binding depends on the duration and severity of cerebral ischemia. Sequential measurements of nimodipine binding may allow the identification of regions with potentially reversible effects of ischemia and the monitoring of their response to therapy.