Bassan Haim, Kidron Debora, Bassan Merav, Rotstein Michael, Kariv Naam, Giladi Eliezer, Davidson Ariane, Gozes Illana, Harel Shaul
Pediatric Neurology and Child Development Unit, Dana Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
J Matern Fetal Neonatal Med. 2010 Jul;23(7):595-600. doi: 10.1080/14767050903197068.
We sought to determine the pathogenesis of neurodevelopmental impairments in survivors of intrauterine growth retardation (IUGR).
We used an experimental rabbit vascular IUGR model. We ligated 25% of uteroplacental vessels (partial ischemia) of one-half of the fetuses on day 25 at the end of the third trimester. We then determined hemispheral DNA and protein levels, and used glial fibrillary acidic protein (GFAP) staining to count the labeled astrocytes at the superficial cortical layers.
Ischemic fetuses were significantly smaller than control fetuses and presented a disproportionately small body and a relatively larger head compared with the normal body/head ratio, confirming the study model as that of asymmetric IUGR. Hemispheral DNA was unchanged in IUGR fetuses, but they had decreased brain weight, hemispheral protein content, and a reduced number of mature (GFAP-positive) cortical astrocytes compared with control fetuses.
Vascular IUGR, as demonstrated in our asymmetric IUGR model, adversely affected brain growth, cell size, and cortical astrocytes maturation. In view of the neurotrophic and neuroprotective functions of astrocytes, a reduced number of mature astrocytes during this critical period of development may be implicated in the pathogenesis of the neurodevelopmental impairments observed in IUGR.
我们试图确定宫内生长受限(IUGR)幸存者神经发育障碍的发病机制。
我们使用了一种实验性兔血管性IUGR模型。在妊娠晚期第25天,将一半胎儿的子宫胎盘血管结扎25%(部分缺血)。然后我们测定半球的DNA和蛋白质水平,并使用胶质纤维酸性蛋白(GFAP)染色来计数表层皮质层标记的星形胶质细胞。
缺血胎儿明显小于对照胎儿,与正常的身体/头部比例相比,身体不成比例地小而头部相对较大,证实该研究模型为不对称性IUGR。IUGR胎儿的半球DNA没有变化,但与对照胎儿相比,他们的脑重量、半球蛋白质含量降低,成熟(GFAP阳性)皮质星形胶质细胞数量减少。
如我们的不对称性IUGR模型所示,血管性IUGR对脑生长、细胞大小和皮质星形胶质细胞成熟产生不利影响。鉴于星形胶质细胞的神经营养和神经保护功能,在这个关键发育时期成熟星形胶质细胞数量减少可能与IUGR中观察到的神经发育障碍的发病机制有关。