Prenatal binge-like alcohol exposure in the rat results in region-specific deficits in brain growth
Prenatal binge-like alcohol exposure in the rat results in region-specific deficits in brain growth
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DOI：
10.1016/s0892-0362(98)00056-7
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发表时间：
1999-05-01
影响因子：
2.9
通讯作者：
West, JR
中科院分区：
文献类型：
--
作者：
Maier, SE;Miller, JA;West, JR
怀孕期间滥用酒精的妇女的孩子可能会受到不同程度的神经异常的影响，即使他们没有被诊断为胎儿酒精综合征。受影响的后代的行为缺陷的程度可能是几个因素的函数，例如大脑不同区域对酒精损伤的不同脆弱性。在本研究中，从胚胎第1天（E1：精子阳性）至E20，将各组定时妊娠大鼠暴露于不同剂量的酒精（EtOH 2.25、EtOH 4.5、EtOH 6.5 g/kg/天）或对照条件（麦芽糖糊精溶液或未处理）。在E33（通常为出生后第10天），对所有幼仔进行灌注。取脑，解剖前脑、小脑和脑干，称重。在妊娠的4个不同日期测量血液酒精浓度（BAC），但对于EtOH 2.25、EtOH 4.5和EtOH 6.5 g/kg组，三个酒精处理组的整个妊娠期间的峰值BAC平均值分别为142、294和413 mg/dl。体重数据分析表明，EtOH 6.5 g/kg组幼仔的躯体生长缺陷大于所有其他组幼仔。尽管EtOH 6.5 g/kg组幼仔的全脑、前脑、小脑和脑干重量显著小于对照组，但给药组内分析表明，EtOH 6.5 g/kg组幼仔的小脑受到的影响比前脑或脑干更严重。脑区与体重比的分析再次显示，EtOH 6.5 g/kg组中幼仔的小脑与体重比受到的影响比前脑或脑干与体重比更严重。总的来说，这些数据支持这样的观点，即大脑的总区域在前两个三个月相当的时间内对酒精损伤的脆弱性不同，并表明小脑在发育期而不是第三个三个月相当的时间内容易受到高BAC的损伤。(C)1999 Elsevier Science Inc. All rights reserved.
Children of women who abuse alcohol during pregnancy may be affected by varying degrees of neurological abnormality, even if they are not diagnosed with Fetal Alcohol Syndrome. The extent of the behavioral deficits of the affected offspring may be a function of several factors, such as the differential vulnerability of the various regions of the brain-to-alcohol insult. In this study, groups of timed-pregnant rats were exposed to different doses of alcohol (EtOH 2.25, EtOH 4.5, EtOH 6.5 g/kg/day) or control conditions (maltose dextrin solution or no treatment) from embryonic day 1 (E1: sperm positive) to E20. On E33 (usually postnatal day 10), all pups were perfused. Their brains were removed, dissected into forebrain, cerebellum and brainstem, and weighed. Blood alcohol concentrations (BACs) were measured on 4 different days of gestation, but the peak BACs across gestation for the three alcohol-treated groups averaged 142, 294, and 413 mg/dl for the EtOH 2.25, EtOH 4.5, and EtOH 6.5 g/kg groups, respectively. Analysis of the body weight data indicated that pups in the EtOH 6.5 g/kg group had a greater somatic growth deficit than pups from all other groups. Although the whole brain, forebrain, cerebellum, and brainstem weights of pups in the EtOH 6.5 g/kg group were significantly smaller than those in the control groups, within-treatment group analyses indicated that the cerebella of pups in the EtOH 6.5 g/kg group were more severely affected than were their forebrains or brainstems. The analyses of the brain region to body weight ratios revealed again that the cerebellum-to-body-weight ratio of pups in the EtOH 6.5 g/kg group was more severely affected than the forebrain or brainstem to body weight ratios. Collectively, these data lend support to the View that gross regions of the brain are differentially vulnerable to alcohol insult during the first two trimesters equivalent, and suggest that the cerebellum is vulnerable to injury from exposure to high BACs during a developmental period other than the third trimester equivalent. (C) 1999 Elsevier Science Inc. All rights reserved.