Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy

Background: The cerebellum of the neonatal rat is highly susceptible to eth anol, with profound loss of Purkinje cells resulting from even brief exposu re during the first postnatal week. Developmental ethanol exposure previous ly has been shown to induce free radicals/oxidative stress processes and/or down-regulate protective antioxidants. In an earlier study, we found antio xidants protected against ethanol neurotoxicity in a tissue culture environ ment. The present study was designed to determine whether similar protectio n could be manifested in the intact: animal. Methods: Neonatal rats were administered a liquid diet via intragastric int ubation on postnatal days 4 and 5 (P4-P5), the peak period of ethanol sensi tivity in the developing cerebellum. The diet consisted of milk formula wit h 12% ethanol, the isocaloric substitution of maltose-dextrin for ethanol, or ethanol plus the antioxidant vitamin E. Unbiased three-dimensional count ing was utilized to analyze Purkinje cell numbers and density within define d volumes from these animals on P5. Results: These determinations revealed a substantial loss of Purkinje cells in the ethanol-treated animals compared to controls (approximately 30-44%) , but this loss was prevented by the inclusion of vitamin E (60IU/100 mi) i n the diet. A lower concentration of the antioxidant (30IU/100 mi) was not effective in this regard, however. Conclusions: These results suggest that ethanol-related cerebellar damage d uring this early postnatal period may be related to oxidative stress proces ses or the insufficiency of protective antioxidants. Thus, antioxidant trea tment may represent a possible therapy for preventing or ameliorating the c entral nervous system (CNS) damage seen in the fetal alcohol syndrome.