Bonthius D J, West J R
Department of Anatomy, University of Iowa, Iowa City 52242.
Alcohol Clin Exp Res. 1990 Feb;14(1):107-18. doi: 10.1111/j.1530-0277.1990.tb00455.x.
A rat model of third trimester fetal alcohol exposure was used to determine whether a smaller daily dose of alcohol can induce more severe microencephaly and neuronal loss than a larger dose, if the small dose is consumed in such a way that it produces higher blood alcohol concentrations (BACs). The possibility of regional differences within the developing brain to alcohol-induced neuronal loss was also investigated. Sprague-Dawley rat pups were reared artificially over postnatal Days 4-10 (a period of rapid brain growth similar to that of the human third trimester). Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 5.1% solution in four of the 12 daily feedings or as a 10.2% solution in two of the 12 feedings. A third group received a higher daily dose (6.6 g/kg) administered as a 2.5% solution in every feeding. Gastrostomy and suckle controls were also reared. On postnatal Day 10, the animals were perfused, and brain weights were obtained. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. In the cerebellum, Purkinje cells and granule cells were counted in each of the ten lobules of the vermis. The lower daily dose (4.5 g/kg) condensed into two or four feedings produced high maximum BACs (means of 361.6 and 190.7 mg/dl, respectively) and significant microencephaly and cell loss, relative to controls. The higher daily dose (6.6 g/kg), administered continuously, resulted in low BACs (mean of 39.2 mg/dl) and induced no microencephaly or cell loss. Regional differences in neuronal vulnerability to alcohol were evident. In the hippocampus, CA1 neuronal number was significantly reduced only by the most condensed alcohol treatment, while CA3, CA4, and the dentate gyrus populations were not reduced with any alcohol treatment. In the cerebellum, some lobules suffered significantly greater Purkinje cell loss and granule cell loss than did others. The regions in which Purkinje cells were most mature at the time of the alcohol exposure were the most vulnerable to Purkinje cell loss.
使用妊娠晚期胎儿酒精暴露的大鼠模型来确定，如果小剂量酒精以产生更高血酒精浓度（BAC）的方式摄入，那么其每日剂量较小时是否比剂量较大时更易诱发更严重的小头畸形和神经元丢失。同时还研究了发育中大脑内酒精诱导的神经元丢失的区域差异。在出生后第4至10天（这一时期大脑快速生长，类似于人类妊娠晚期）对斯普拉格-道利大鼠幼崽进行人工饲养。两组大鼠每日酒精剂量为4.5 g/kg，一组在12次每日喂食中的4次喂食时给予5.1%的溶液，另一组在12次喂食中的2次喂食时给予10.2%的溶液。第三组大鼠每日接受更高剂量（6.6 g/kg），每次喂食时给予2.5%的溶液。还饲养了胃造口和哺乳对照大鼠。在出生后第10天，对动物进行灌注，并测量脑重量。在海马结构中，对CA1区和CA2/3区的锥体细胞、CA4区的多种细胞类型以及齿状回的颗粒细胞进行细胞计数。在小脑，对蚓部的十个小叶中的浦肯野细胞和颗粒细胞进行计数。相对于对照组，浓缩在两次或四次喂食中的较低每日剂量（4.5 g/kg）产生了较高的最大BAC（分别为361.6和190.7 mg/dl），并导致了显著的小头畸形和细胞丢失。连续给予的较高每日剂量（6.6 g/kg）导致低BAC（平均为39.2 mg/dl），未诱发小头畸形或细胞丢失。神经元对酒精的易损性存在区域差异。在海马中，只有最浓缩的酒精处理显著减少了CA1神经元数量，而CA3、CA4和齿状回的细胞数量在任何酒精处理下均未减少。在小脑中，一些小叶的浦肯野细胞丢失和颗粒细胞丢失比其他小叶明显更严重。在酒精暴露时浦肯野细胞最成熟的区域最易发生浦肯野细胞丢失。
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