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Journal of Korean Neurosurgical Society > Volume 24(6); 1995 > Article
Journal of Korean Neurosurgical Society 1995;24(6): 631-639.
The Neuroprotective Effects of Phenytion on Ischemic-hypoxic Injury to the Developing Rat Brain.
Young Baeg Kim, Eun Sub Park, Young Hwan Ahn, Kwan Park, Byung Kook Min, Sung Nam Hwang, Jong Sik Suk, Duck Young Choi
1Department of Neurosurgery, College of Medicine Chung-Ang University, Seoul, Korea.
2Department of Pathology, College of Medicine Chung-Ang University, Seoul, Korea.
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.
Key Words: Neuroprotection; Phenytoin; Ischemia; Hypoxia; Developing brain
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