The Neuroprotective Effects of Phenytion on Ischemic-hypoxic Injury to the Developing Rat Brain

ABSTRACT

Phenytoin is an anticonvulsant compound which modulates the voltage-dependent sodium channels. It has a neuroprotective effect in vitro against hypoxic damage in hippocampal slices of adult rats. The authors studied the efficacy of phenytion on cerebral ischemia in an vivo model of hypoxic-ischemic brain injury in developing rat brain. To elicit injury, 7 days old(P7) Sprague-dawley rats subjected to right common carotid ligation followed by 8% O2 exposure(humidified, balanced with nitrogen) for 3 hours under the halothane anesthesia(control group, N=58). Body temperature of the rats was accurately controlled before and during hypoxia. Before hypoxia, pups received intraperitoneal phenytoin(30mg/kg)(phenytoin-treated group, N=17). The animals were sacrificed one week later and histopathological evaluation of ischemic neuronal damage were conducted employing hematoxylin-eosin staining and measurement of the hemispheric weight differences were performed. Phenytoin was found to be effective in reducing neuronal damage in terms of weight comparison(24+/-2.4% atrophy of control vs. 5+/-2.9% atrophy of phenytoin group, p<0.001) and ischemic changes in hippocampal region(p<0.05 in CA1, CA2, and CA3 area). These data suggest that compounds like phenytoin, which modulates voltage-dependent sodium channels, can reduce the degree of injury from hypoxic-ischemic insults to the developing rat brain.