Therapeutic Effect of Nimodipine in Neonatal Rat Model of Cerebral Hypoxia-Ischemia

Hong, Ihn Hee; Kim, Heng Mi

Abstract

PURPOSE: Recent studies suggest that nimodipine, a potent calcium-channel blocker, may improve neurological outcome after experimental hypoxia-ischemic brain injury. This study was conducted to evaluate the therapeutic effect of nimodipine on hypoxia-ischemia in immature rat brain.
METHODS
Seven-day postnatal rats were subjected to hypoxia-ischemia by unilateral common carotid artery occlusion combined with 2 hours of hypoxia(in 8% oxygen at an ambient temperature of 36degrees C). Then 20 rats received an intraventricular injection of nimodipine while the remaining 23 rats were injected with saline. Histologic examinations and morphometric analyses of brain tissue specimens were carried out 2 weeks after the hypoxia-ischemia.
RESULTS
Histopathological analysis of each rat showed that the brains of the nimodipine-treated animals were less damaged when compared with control rats treated with saline. Fifty percent of nimodipine treated rats but only 13% of saline-treated rats revealed normal histologic findings(P< 0.05). Gliosis &/or nerve cell necrosis were observed, over three brain lobes in 15% of nimodipine-treated rats and 57% of saline-treated rats respectively(P<0.05). At the level of dorsal hippocampus, saline-treated rats revealed 0.18+/-0.17mm smaller ipsilateral cerebral hemispheres than contralateral hemispheres to artery dissections but nimodipine-treated rats showed only 0.07+/-0.14mm smaller hemispheres(P<0.05). The difference between contralateral and ipsilateral cerebral cortex was 0.4+/-0.36mm in saline-treated rats and 0.11+/-0.14mm in nimodipine-treated rats(P<0.05). The contraction of cerebral hemisphere and cortex were significantly reduced in nimodipine-treated rats.
CONCLUSION
The finding indicates that post-insult nimodipine treatment in the immature rat decreases the extent of hypoxic-ischemic brain damage.