Fetal alcohol exposure and temporal vulnerability regional differences in alcohol-induced microencephaly as a function of the timing of binge-like alcohol exposure during rat brain development.
Fetal alcohol exposure and temporal vulnerability regional differences in alcohol-induced microencephaly as a function of the timing of binge-like alcohol exposure during rat brain development.
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DOI：
10.1111/j.1530-0277.1997.tb04471.x
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发表时间：
1997-11
期刊：
影响因子：
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通讯作者：
S. E. Maier;Wei-Jung A. Chen;Jennifer A. Miller;James R. West
中科院分区：
文献类型：
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作者：
S. E. Maier;Wei-Jung A. Chen;Jennifer A. Miller;James R. West
在人类中，小头畸形（与身体大小相比头小）是胎儿酒精综合征的常见特征。一种类似的测量方法，称为小脑畸形（相对于身体大小的小大脑），可用于评估不同时间酒精暴露对动物模型系统大脑发育的有害影响。定时怀孕的大鼠在妊娠的前10天（孕早期等效）或妊娠的后10天（孕中期等效）或孕早期和孕中期等效的组合中暴露于酒精中进行产前治疗。在孕早期和孕中期接触酒精的一些动物的后代从出生后第4天(P)到第9天（孕晚期的一部分）被人工饲养，并在此期间接受类似狂欢的酒精治疗，产生的动物在孕早期和孕中期都接触酒精。未经处理的水坝的后代也被人工饲养，从P4到P9只接受酒精，从而创造了只在妊娠晚期的部分时间接触酒精的动物。所有幼崽均在P10灌注。每个酒精处理组合采用适当的对照（营养对照和正常饲养对照）。在给定的采样时间内，治疗组之间的血液酒精浓度峰值没有差异。与在其他时期暴露于酒精的后代相比，暴露于酒精的后代在相当于所有三个月的时间里都出现了显著的躯体生长缺陷。后代的大脑发育也受到酒精暴露时间的显著影响。在妊娠晚期接触酒精的幼崽的整个大脑、前脑和小脑与体重的比例比在其他大脑发育时期接触酒精的幼崽有更显著的大脑发育缺陷。虽然在妊娠晚期接触酒精对大脑的整体发育有显著的不利影响，但脑干与体重的时间脆弱性也存在显著差异。妊娠前三个月接触酒精的母鼠后代与妊娠晚期接触酒精的母鼠后代的缺陷程度相同，与其他时间接触酒精的母鼠相比，这两组的缺陷程度显著不足，表明该区域在不同发育时期对酒精损伤的易损性存在差异。这项研究首次在动物模型系统中对酒精暴露的时间因素与小脑畸形和发育中的大脑的总体区域脆弱性进行了彻底的检查，其结果支持并扩展了现有临床文献的发现。此外，我们的研究结果证实了在妊娠晚期之前停止饮酒可以减轻一些与酒精相关的出生缺陷的严重程度。
In humans, microcephaly (small head for body size) is a common feature of fetal alcohol syndrome. An analogous measure, termed microencephaly (small brain for body size), can be used for evaluating the detrimental effects of the differential timing of alcohol exposure on brain development in animal model systems. Timed-pregnant rats were exposed to binge-like alcohol during either the first 10 days (first trimester equivalent) or second 10 days of gestation (second trimester equivalent), or the combination of first and second trimesters equivalent for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first and second trimesters equivalent were raised artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent), and also received binge-like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also raised artificially and received alcohol only from P4 to P9, thus creating animals that were exposed to alcohol only during part of the third trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were used for every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Significant somatic growth deficits occurred in offspring exposed to alcohol for the equivalent of all three trimesters, compared with offspring exposed to alcohol during other periods. Brain growth in offspring also was significantly affected by the timing of alcohol exposure. The whole brain, forebrain, and cerebellum to body weight ratios of pups exposed to alcohol during the third trimester had more significant brain growth deficits than pups in groups exposed to alcohol during other times of brain development. Although alcohol exposure during the third trimester had a significant detrimental impact on overall brain growth, significant differences in temporal vulnerability were also found for the brainstem to body weight ratios. Offspring of dams exposed to alcohol during the first trimester had the same magnitude of deficit as those exposed to alcohol during the third trimester, and those two groups were significantly deficient compared with the groups exposed to alcohol at other times, suggesting some differential vulnerability of this region to alcohol-induced injury at different times of development. This study is the first thorough examination of microencephaly and gross regional vulnerability of the developing brain as related to temporal factors of alcohol exposure in an animal model system, and the results support and expand on the findings of the available clinical literature. Furthermore, our results substantiate claims that the cessation of alcohol before the third trimester can lessen the severity of some alcohol-related birth deficits.