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

被引:59
作者
Heaton, MB
Mitchell, JJ
Paiva, M
机构
[1] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA
[2] Univ Florida, Alcohol Res Ctr, Inst Brain, Dept Neurosci, Gainesville, FL 32610 USA
关键词
fetal alcohol syndrome; neurotoxicity; neuroprotection; antioxidants; alpha-tocopherol; vitamin E; cerebellum; Purkinje cells;
D O I
10.1097/00000374-200004000-00026
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Background: The cerebellum of the neonatal rat is highly susceptible to ethanol, with profound loss of Purkinje cells resulting from even brief exposure during the first postnatal week. Developmental ethanol exposure previously has been shown to induce free radicals/oxidative stress processes and/or down-regulate protective antioxidants. In an earlier study, we found antioxidants protected against ethanol neurotoxicity in a tissue culture environment. The present study was designed to determine whether similar protection could be manifested in the intact: animal. Methods: Neonatal rats were administered a liquid diet via intragastric intubation on postnatal days 4 and 5 (P4-P5), the peak period of ethanol sensitivity in the developing cerebellum. The diet consisted of milk formula with 12% ethanol, the isocaloric substitution of maltose-dextrin for ethanol, or ethanol plus the antioxidant vitamin E. Unbiased three-dimensional counting was utilized to analyze Purkinje cell numbers and density within defined 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) in 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 during this early postnatal period may be related to oxidative stress processes or the insufficiency of protective antioxidants. Thus, antioxidant treatment may represent a possible therapy for preventing or ameliorating the central nervous system (CNS) damage seen in the fetal alcohol syndrome.
引用
收藏
页码:512 / 518
页数:7
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