Protective effect of nimodipine on behavior and white matter of rats with hydrocephalus.
OBJECTIVE
Hydrocephalus, a pathological dilation of the ventricles of the brain, causes damage to periventricular white matter, at least in part, through chronic ischemia. The authors tested the hypothesis that treatment with nimodipine, an L-type calcium channel-blocking agent with demonstrated efficacy 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 kaolin into the cisterna magna. The rats were treated by continuous administration of nimodipine or control vehicle for 2 weeks, beginning 2 weeks after induction of hydrocephalus. During the treatment period, the animals underwent repeated tests of motor and cognitive behavior. At the end of the treatment period, the rat brains were analyzed by histopathological and biochemical means. 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 equal in the two groups, although the corpus callosum was thicker in the treated rats. Myelin content in white matter and synaptophysin content in gray matter, an indicator of synapses, did not differ.


CONCLUSIONS
The protective effect of nimodipine is most likely based on improved blood flow, although prevention of calcium influx-mediated proteolytic processes in axons cannot be excluded. Adjunctive pharmacological therapy may be beneficial to patients with hydrocephalus.
Del Bigio
M R
MR
Department of Pathology, University of Manitoba, Winnipeg, Canada. delbigi@cc.umanitoba.ca
Massicotte
E M
EM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006849:Hydrocephalus / Q000188:drug therapy* / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D009412:Nerve Fibers / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D009553:Nimodipine