Ryabinin A E, Cole M, Bloom F E, Wilson M C
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Alcohol Clin Exp Res. 1995 Jun;19(3):784-91. doi: 10.1111/j.1530-0277.1995.tb01583.x.
The artificial rearing model (AR) of fetal alcohol syndrome (FAS) has been shown to induce several major pathologies in the early postnatal rat brain development: microcephaly, selective neuronal cell loss, and activation of astroglia in the neocortex. The purpose of this study was to determine whether these pathologies were specific to the action of alcohol or, in contrast, could result from confounds attributed to this model of FAS. For this purpose, the pathological effects of AR were compared with those of a vapor inhalation (VI) model of FAS. Our studies showed that the microcephaly that developed after exposure to periodic blood alcohol levels (BALs) of 300-350 mg% during postnatal days 4-9 could be achieved by both AR and IV models of FAS, and thus is independent of the method of alcohol administration. In contrast, the gliosis measured by glial fibrillary acidic protein (GFAP) mRNA levels in cortex, as well as by immunohistochemical staining for GFAP, was found only in the AR-FAS model, but not in the VI model. However, the lack of gliosis in VI was apparently not due to a less intrusive intervention of alcohol, because VI exposure resulted in a reduction in Purkinje cell number comparable with that found after AR or intragastric intubation of alcohol. Based on these observations, we conclude that the activation of gliosis observed after AR is not a specific effect of alcohol, but rather is caused by an interaction of alcohol with as yet unidentified factors present in AR.
胎儿酒精综合征（FAS）的人工饲养模型（AR）已被证明在出生后早期大鼠大脑发育中会诱发几种主要病变：小头畸形、选择性神经元细胞丢失以及新皮质中星形胶质细胞的激活。本研究的目的是确定这些病变是否特定于酒精的作用，或者相反，是否可能由该FAS模型的混杂因素导致。为此，将AR的病理效应与FAS的蒸汽吸入（VI）模型的病理效应进行了比较。我们的研究表明，在出生后第4至9天暴露于300 - 350mg%的周期性血酒精水平（BALs）后出现的小头畸形，可通过FAS的AR和IV模型实现，因此与酒精给药方法无关。相比之下，通过皮质中胶质纤维酸性蛋白（GFAP）mRNA水平以及GFAP免疫组织化学染色测量的胶质增生仅在AR - FAS模型中发现，而在VI模型中未发现。然而，VI中缺乏胶质增生显然不是由于酒精的干预性较小，因为VI暴露导致浦肯野细胞数量减少，与AR或酒精灌胃后观察到的情况相当。基于这些观察结果，我们得出结论，AR后观察到的胶质增生激活不是酒精的特定作用，而是由酒精与AR中存在的尚未确定的因素相互作用引起的。
