Stiefel Dorothea, Meuli Martin
Neural Development Unit, Institute of Child Health, University College London, London, WC1N 1EH United Kingdom.
J Pediatr Surg. 2007 Sep;42(9):1561-5. doi: 10.1016/j.jpedsurg.2007.04.019.
Previous studies demonstrated that the spinal cord within a fetal myelomeningocele (MMC) lesion suffers progressive destruction during gestation. This study aims at elucidating this pathophysiologic feature on a cellular and ultrastructural level in a model of genetically determined MMC.
Curly tail/loop tail mouse fetuses at various gestational stages and neonates were analyzed electron-microscopically to document time-point and nature of neural tissue development and pathologic alterations within the MMC.
At embryonic day (E) 8.5 and E9.5, round cells displaying multiple microvilli covered the entire region of interest, and some specimens showed initial stages of neurulation. At E10.5, neurulation was terminated in normal animals, whereas the neural placode remained unfolded in MMC fetuses and became distinguishable from adjacent epidermal layers. At E15.5, an apparently normal differentiation was found. Until this time-point, there was no tissue damage or inflammation. Thereafter, increasingly severe tissue alterations were identified with ongoing gestation leading to almost complete loss of neural tissue at birth.
We show here in fetal mice with MMC that, apart from absent neurulation, growth and development of the otherwise perfectly intact exposed spinal cord appear normal in early gestation, whereas later, the unprotected neural tissue is progressively destroyed.
先前的研究表明，胎儿脊柱裂（MMC）病变内的脊髓在妊娠期会遭受渐进性破坏。本研究旨在通过基因决定的MMC模型，在细胞和超微结构水平上阐明这一病理生理特征。
对不同妊娠阶段的卷尾/环尾小鼠胎儿和新生儿进行电子显微镜分析，以记录MMC内神经组织发育的时间点和性质以及病理改变。
在胚胎第（E）8.5天和E9.5天，显示多个微绒毛的圆形细胞覆盖了整个感兴趣区域，一些标本显示出神经胚形成的初始阶段。在E10.5天，正常动物的神经胚形成终止，而MMC胎儿的神经板仍未展开，并与相邻的表皮层区分开来。在E15.5天，发现明显正常的分化。直到这个时间点，没有组织损伤或炎症。此后，随着妊娠的进行，越来越严重的组织改变被识别出来，导致出生时神经组织几乎完全丧失。
我们在此表明，在患有MMC的胎儿小鼠中，除了神经胚形成缺失外，在妊娠早期，原本完全完整的暴露脊髓的生长和发育似乎正常，而在后期，未受保护的神经组织会逐渐被破坏。
