All three trimester binge alcohol exposure causes fetal cerebellar Purkinje cell loss in the presence of maternal hypercapnea, acidemia, and normoxemia:: Ovine model
All three trimester binge alcohol exposure causes fetal cerebellar Purkinje cell loss in the presence of maternal hypercapnea, acidemia, and normoxemia:: Ovine model
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DOI：
10.1111/j.1530-0277.2007.00422.x
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发表时间：
2007-07-01
影响因子：
3.2
通讯作者：
Cudd, Timothy A.
中科院分区：
文献类型：
--
作者：
Ramadoss, Jayanth;Lunde, Emilie R.;Cudd, Timothy A.
背景资料：在大鼠和绵羊模型中，晚期妊娠相当于小脑对酒精介导的损伤的脆弱期。我们希望确定是否在整个妊娠期暴露于酒精的结果更大的伤害相比，暴露仅限于第三个三月当量。虽然之前已经在大鼠模型中解决了这个问题，其中第三个三个月的等效发生在出生后，但尚未在动物模型中解决，其中所有3个三个三个月的等效发生在产前，如绵羊。我们还希望相关小脑浦肯野细胞损失酒精介导的母体动脉pH值和血气的改变，因为这些反应可能是重要的机械介导的damage.Methods：三组怀孕的绵羊：未经处理的正常对照组，生理盐水对照组，和酒精组（1.75克/公斤体重）。酒精暴露方案的设计是为了模仿人类的狂欢模式;酒精是连续3天静脉注射，然后4天没有酒精，从妊娠第4天开始，持续到妊娠第132天，相当于人类大脑生长的晚期妊娠结束。与对照组相比，所有3个月的酒精暴露胎脑小脑体积和浦肯野细胞数量显着不足。我们没有检测到的浦肯野细胞数量的减少之间的比较时，所有3个月和妊娠晚期酒精暴露研究的差异。神经元的损失是伴随着母亲的高碳酸血症，酸血症，和normoxemia.Conclusions：这些研究结果表明，在绵羊模型中，所有3个月相当于大脑生长发生在子宫内，胎儿小脑浦肯野细胞更敏感的酒精暴露的时间，所以曝光的持续时间。未检测到母体PaO 2降低，表明母体缺氧在胎儿浦肯野细胞丢失中不起作用。最后，我们得出结论，酒精引起的母体动脉pH值的变化可能在酒精介导的发育性脑损伤中发挥作用。
Background: The third trimester equivalent has been identified, both in rat and sheep models, as a period of cerebellar vulnerability to alcohol-mediated injury. We wished to determine whether alcohol exposure throughout gestation results in greater injury compared with exposure limited to the third trimester equivalent. While this question has previously been addressed in the rat model, where the third trimester equivalent occurs postnatally, it has not yet been addressed in an animal model where all 3 trimester equivalents occur prenatally, as in the ovine. We also wished to correlate cerebellar Purkinje cell loss to alcohol-mediated alterations in maternal arterial pH and blood gases as these responses might be important mechanistically in mediating the damage.Methods: Three groups of pregnant sheep were used: an untreated normal control group, a saline control group, and an alcohol group (1.75 g/kg of the body weight). The alcohol exposure regimen was designed to mimic a human binge pattern; alcohol was administered intravenously on 3 consecutive days, followed by 4 days without alcohol, beginning day 4 of gestation, continuing to the end of the third trimester equivalent of human brain growth, day 132 of gestation.Results: All 3 trimester alcohol-exposed fetal brains exhibited significant deficits in cerebellar volume and Purkinje cell number compared with those of control subjects. We did not detect a difference in the reduction of Purkinje cell number when comparing between all 3 trimester and third trimester alcohol exposure studies. The neuronal loss was accompanied by maternal hypercapnea, acidemia, and normoxemia.Conclusions: These findings demonstrate in an ovine model where all 3 trimester equivalent of brain growth occur in utero that the fetal cerebellar Purkinje cells are more sensitive to the timing of alcohol exposure and less so to the duration of exposure. Decreases in maternal PaO2 were not detected, suggesting that maternal hypoxia does not play a role in fetal Purkinje cell loss. And finally, we conclude that alcohol-induced changes in maternal arterial pH may play a role in alcohol-mediated developmental brain injury.