Misztal D R, Ashwell K W, Zhang L L
School of Anatomy, University of NSW, Australia.
Neurotoxicol Teratol. 1994 Nov-Dec;16(6):593-603. doi: 10.1016/0892-0362(94)90037-x.
Prenatal exposure to the drug methylazoxy-methanol acetate (MAM Ac) has been commonly used as an experimental model of prenatal cytotoxic brain damage. We have examined the effects of this prenatal brain damage on the development of vasculature in the fetal neocortex, because vasculature is likely to play an important role in fetal brain repair. Pregnant Wistar strain rats received either MAM Ac (25 mg/kg) or saline on embryonic day (E) 13 by IP injection. At E15, E17, E19, and and E21, the rats were overdosed with pentobarbitone (100 mg/kg) and fetuses removed for paraffin embedding, lectin histochemistry, and electron microscopy. For lectin histochemistry, sections were exposed to a horseradish peroxidase-conjugated B4 isolectin from Griffonia simplicifolia. Fetuses exposed to MAM Ac showed significant deficits in cortical vessel branch point density at E15 and E17 (46% and 20%, respectively). There were also significant reductions in stem vessel density at these ages (34% and 26%, respectively) among MAM Ac exposed animals, but there were no differences in growing tip density, capillary internal diameter, or stem vessel internal diameter. The only consistent differences between the two groups at the electron microscope level were an increase in vacuolisation and an irregular luminal surface in MAM Ac animals at E15. Tight junction formation, basement membrane formation, and loss of fenestrations were not delayed in experimental animals. The results indicate that there is no increase in angiogenic activity coincident with the fetal neocortical repair that follows MAM Ac induced damage.
产前暴露于药物乙酸甲基偶氮甲醇（MAM Ac）已被广泛用作产前细胞毒性脑损伤的实验模型。我们研究了这种产前脑损伤对胎儿新皮质血管发育的影响，因为血管可能在胎儿脑修复中发挥重要作用。怀孕的Wistar品系大鼠在胚胎第13天通过腹腔注射接受MAM Ac（25 mg/kg）或生理盐水。在胚胎第15天、17天、19天和21天，给大鼠过量注射戊巴比妥（100 mg/kg），取出胎儿进行石蜡包埋、凝集素组织化学和电子显微镜检查。对于凝集素组织化学，切片用来自西非豆的辣根过氧化物酶偶联B4异凝集素处理。暴露于MAM Ac的胎儿在胚胎第15天和17天的皮质血管分支点密度显著降低（分别为46%和20%）。在这些年龄段，暴露于MAM Ac的动物的主干血管密度也显著降低（分别为34%和26%），但生长尖端密度、毛细血管内径或主干血管内径没有差异。在电子显微镜水平上，两组之间唯一一致的差异是胚胎第15天MAM Ac处理动物的空泡化增加和管腔表面不规则。实验动物的紧密连接形成、基底膜形成和窗孔丧失并未延迟。结果表明，在MAM Ac诱导损伤后的胎儿新皮质修复过程中，血管生成活性没有增加。
