Sulik K K, Lauder J M, Dehart D B
Department of Anatomy, School of Medicine, University of North Carolina, Chapel Hill, NC 27514, U.S.A.; Department of Ophthalmology, School of Medicine, University of North Carolina, Chapel Hill, NC 27514, U.S.A.
Department of Anatomy, School of Medicine, University of North Carolina, Chapel Hill, NC 27514, U.S.A.
Int J Dev Neurosci. 1984;2(3):203-14. doi: 10.1016/0736-5748(84)90014-5.
Acute maternal ethanol administration (two i.p. injections of 2.9 g ethanol/kg maternal body wt) to C57B1/6J mice during gastrulation stages of embryogenesis (gestational day 7) induces a spectrum of brain and facial malformations characteristic of those seen in the human Fetal Alcohol Syndrome. Scanning electron microscopic and light microscopic analyses of the brains of embryos of gestational days 11-14 demonstrate ventro-medial forebrain deficiencies of varying degrees of severity in affected specimens. Even at the mild end of the spectrum, reductions in the size of the septal nuclei and the shape of the third ventricle are observed. As the severity of the effect increases, the septal nuclei disappear altogether, resulting in midline fusion of the corpora striata (basal ganglia). In such cases, the third ventricle is totally absent anteriorly (preoptic area) and significantly narrowed at more posterior levels, adjacent to the ventromedial nuclei. In addition, the hippocampal primordium is absent at levels which include the corpora striata, and septation of the cerebral cortex is incomplete. More posteriorly, at the level of the posterior commissure, the hippocampal primordium is present, but greatly reduced in size, and the entire brain is distinctly narrower in width. Still further posteriorly, at levels of the metencephalon which include the tectum and cerebellar plate, the cerebral aqueduct is significantly expanded, fusion of midline (raphe) structures is incomplete and the cerebellar plate does not extend as far medially as it does normally. Interestingly, these abnormalities are analogous to those observed in the holoprosencephaly series of malformations. The results of the present study support our hypothesis that severe forms of the Fetal Alcohol Syndrome mimic certain aspects of the holoprosencephaly spectrum, and indicate that special attention should be paid to possible deficiencies in the septal nuclei and basal ganglia of children born to women who abuse alcohol. The fact that gross brain malformations can be induced in this animal model at a time corresponding to the third week of human gestation (a time when most women remain unaware of pregnancy) is of significance in terms of the possible prevention of alcohol-induced birth defects and mental deficiency in man.
在胚胎发育的原肠胚形成阶段（妊娠第7天），给C57B1/6J小鼠急性腹腔注射乙醇（两次，每次剂量为2.9克乙醇/千克母体体重），会诱发一系列大脑和面部畸形，这些畸形是人类胎儿酒精综合征所特有的。对妊娠第11 - 14天胚胎大脑的扫描电子显微镜和光学显微镜分析表明，受影响的标本存在不同程度严重的腹内侧前脑缺陷。即使在症状较轻的情况下，也可观察到隔核尺寸减小以及第三脑室形状改变。随着影响严重程度的增加，隔核完全消失，导致纹状体（基底神经节）中线融合。在这种情况下，第三脑室在前方（视前区）完全缺失，在更靠后的水平，与腹内侧核相邻处明显变窄。此外，在包括纹状体的水平，海马原基缺失，大脑皮质分隔不完全。在更靠后的后连合水平，海马原基存在，但尺寸大大减小，整个大脑宽度明显变窄。再往后，在包括顶盖和小脑板的后脑水平，中脑导水管明显扩张，中线（缝际）结构融合不完全，小脑板不像正常那样向内侧延伸那么远。有趣的是，这些异常与全前脑畸形系列中观察到的异常相似。本研究结果支持我们的假设，即严重形式的胎儿酒精综合征模仿了全前脑畸形谱的某些方面，并表明应特别关注酗酒妇女所生孩子的隔核和基底神经节可能存在的缺陷。在这个动物模型中，在相当于人类妊娠第三周（此时大多数妇女仍未意识到怀孕）的时间可诱发明显的大脑畸形，这对于预防人类酒精诱导的出生缺陷和智力缺陷具有重要意义。
