All issues > Volume 42(11); 1999

Original Article

J Korean Pediatr Soc. 1999;42(11):1552-1558. Published online November 15, 1999.

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

Ihn-Hee IH Hong¹, Heng-Mi HM Kim¹

¹Department of Pediatrics, School of Medicine, Kyungpook University, Taegu, Korea

Correspondence Ihn-Hee IH Hong ,Email: 1

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 36℃). 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.

Keywords :Nimodipine, Calcium channel blocker, Hypoxia-Ischemia, Neonatal rat