Reis Joaquim L, Correia-Pinto Jorge, Monteiro Mariana P, Hutchins Grover M
Department of Anatomy, Abel Salazar Institute for Biomedical Sciences (ICBAS) and Unit for Multidisciplinary for Biomedical Research (UMIB), University of Porto, Portugal.
J Neurosurg. 2007 Jun;106(6 Suppl):472-9. doi: 10.3171/ped.2007.106.6.472.
Myelomeningocele (MMC) is the most severe form of spina bifida causing severe neurological deficits. Injury to the placode has been attributed to in utero aggression. In this study, glial and neuronal cell changes in both number and topography in mice with MMC were investigated during gestation.
The curly tail/loop-tail mice model of MMC was used, and fetuses were harvested using caesarean surgery at Days 14.5, 16.5, and 18.5 (full gestation at 19 days). Immunohistochemical analyses of the MMC placodes and the normal spinal cords from the control group were performed using anti-glial fibrillary acidic protein (astrocytes) and mouse anti-neuronal nuclear (neurons) antibodies. Light microscopy was used along with computer-assisted morphometric evaluation. Progressive increases in astrocytes in the spinal cord of all mouse fetuses were found between Days 14.5 and 18.5 of gestation. This increase was significantly higher in the placodes of mice with MMC than in those of normal mice, particularly in the posterior region. Neuronal labeling at Day 14.5 of gestation was similar between mice with MMC and control mice. At Day 16.5 of gestation there was a deterioration of neural tissue in MMC fetuses, mainly in the posterior region, progressing until the end of gestation with a marked loss of neurons in the entire MMC placode.
This study delineated the quantitative changes in astrocytes and neurons associated with MMC development during the late stages of gestation. The detailed topographic analysis of the MMC defines the timing of the intrauterine insult and how the placode lesions progress. This study supports the current concept of placode protection through in utero surgery for fetuses with MMC.
脊髓脊膜膨出（MMC）是脊柱裂最严重的形式，可导致严重的神经功能缺损。神经板损伤被认为与子宫内的侵害有关。在本研究中，对妊娠期患有MMC的小鼠神经胶质细胞和神经元细胞数量及拓扑结构的变化进行了研究。
采用MMC的卷尾/环尾小鼠模型，在妊娠第14.5天、16.5天和18.5天（妊娠全程为19天）通过剖腹产手术获取胎儿。使用抗胶质纤维酸性蛋白（星形胶质细胞）和小鼠抗神经元核（神经元）抗体对MMC神经板和对照组的正常脊髓进行免疫组织化学分析。使用光学显微镜并结合计算机辅助形态学评估。发现在妊娠第14.5天至18.5天期间，所有小鼠胎儿脊髓中的星形胶质细胞逐渐增加。这种增加在患有MMC的小鼠神经板中比正常小鼠神经板中显著更高，特别是在后部区域。妊娠第14.5天时，患有MMC的小鼠和对照小鼠之间的神经元标记相似。在妊娠第16.5天时，MMC胎儿的神经组织出现退化，主要在后部区域，这种退化一直持续到妊娠末期，整个MMC神经板中的神经元明显丢失。
本研究描述了妊娠后期与MMC发育相关的星形胶质细胞和神经元的定量变化。对MMC进行详细的拓扑分析确定了子宫内损伤的时间以及神经板病变的进展方式。本研究支持通过对患有MMC的胎儿进行子宫内手术来保护神经板的当前概念。
