Nimodipine increases blood-brain barrier permeability after cerebral ischemia and reperfusion in rats

Abstract

Objective To study the effect of nimodipine on the blood-brain barrier (BBB) permeability and cerebral infarct volume in mrs after cerebral ischemia and reperfusion. Methods Cerebral ischemia-reperfusion injury was induced by a 2-hour suture occlusion of the unilateral middle cerebral artery followed by reperfusion in 150 rats which were randomized into nimodipine and normal saline groups. Immediately after suture withdrawal to allow reperfusion, the two groups of rats were subjected to intraperitoneal injections of 2 mg/kg nimodipine (nimodipine group) or normal saline (saline group) at a 12-hour interval. At the time points of 6, 12, 24, 48 and 72 h after the reperfusion, the BBB permeability of the rats was evaluated with fluorophotometry and transmission electron microscopy, and the infect volume was estimated using TTC staining. Results The BBB permeability and the percentage of cerebral infarct volume increased gradually with prolonged reperfusion, and the BBB permeability presented with two peak increment occurring at 12 and 48 h of reperfusion, respectively. Nimodipine injection significantly increased the BBB permeability and the infarct volume in comparison with those in the saline group (P<0.05). Conclusion Cerebral ischemia and reperfusion destroys the integrity of the BBB and aggravates the ischemic cerebral infarction in rats, and the use of nimodipine after reperfusion further worsens these pathologies. Key words: Cerebral ischemia-reperfusion; Blood-brain barrier; Nimodipine