Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy
Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy
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DOI：
10.1111/j.1530-0277.2000.tb02019.x
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发表时间：
2000-04-01
影响因子：
3.2
通讯作者：
Paiva, M
中科院分区：
文献类型：
--
作者：
Heaton, MB;Mitchell, JJ;Paiva, M
背景资料：新生大鼠的小脑对乙醇高度敏感，即使在出生后第一周短暂暴露也会导致浦肯野细胞的严重损失。先前已证明发育中的乙醇暴露可诱导自由基/氧化应激过程和/或下调保护性抗氧化剂。在早期的研究中，我们发现抗氧化剂可以在组织培养环境中保护乙醇神经毒性。本研究的目的是确定是否可以表现出类似的保护在完整的：animal.Methods：新生大鼠通过胃内插管在出生后第4和第5天（P4-P5），乙醇敏感性的高峰期，在发展中的小脑的流质饮食。饮食包括含12%乙醇的牛奶配方，等热量的麦芽糖糊精替代乙醇，或乙醇加抗氧化剂维生素E。结果：与对照组相比，乙醇组动物的浦肯野细胞数量明显减少（约30-44%），但饲料中添加维生素E（60 IU/100 ml）可防止这种损失。较低浓度的抗氧化剂（30 IU/100 mi）在这方面是没有效果的，然而，结论：这些结果表明，乙醇相关的小脑损伤在此早期出生后的时期可能与氧化应激过程或保护性抗氧化剂不足。因此，抗氧化剂治疗可能是一种可能的治疗，用于预防或改善中枢神经系统（CNS）的损害中看到的胎儿酒精综合征。
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.