Protective effect of nimodipine on behavior and white matter of rats with hydrocephalus

Object. Hydrocephalus, a pathological dilation of the ventricles of the bra in, causes damage to periventricular white matter, at least in part, throug h chronic ischemia. The authors tested the hypothesis that treatment with n imodipine, an L-type calcium channel-blocking agent with demonstrated effic acy in a range of cerebral ischemic disorders, would ameliorate the adverse effects of experimental hydrocephalus. Methods. Hydrocephalus was induced in 3-week-old rats by injection of kaoli n into the cisterna magna. The rats were treated by continuous administrati on of nimodipine or control vehicle for 2 weeks, beginning 2 weeks after in duction of hydrocephalus. During the treatment period, the animals underwen t repeated tests of motor and cognitive behavior. At the end of the treatme nt period, the rat brains were analyzed by histopathological and biochemica l mans. Nimodipine treatment prevented the declines in motor and cognitive behavior that were observed in untreated control rats. During the treatment period, ventricular enlargement, determined by magnetic resonance imaging, was equ al in the two groups, although the corpus callosum was thicker in the treat ed rats. Myelin content in white matter and synaptophysin content in gray m atter, an indicator of synapses, did not differ. Conclusions. The protective effect of nimodipine is most likely based on im proved blood flow, although prevention of calcium influx-mediated proteolyt ic processes in axons cannot be excluded. Adjunctive pharmacological therap y may be beneficial to patients with hydrocephalus.