PDF(Pubmed)
Abstract：
Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.
摘要：
胎儿生长受限（FGR）与子宫胎盘功能不全有关，以及婴儿的神经发育和结构性大脑缺陷。目前是无法治愈的。我们假设用血管内皮生长因子腺病毒基因治疗（Ad。VEGF-A165）使豚鼠FGR模型中的后代脑重量正常化并防止脑损伤。怀孕的豚鼠在受孕前后饲喂限制饮食并接受Ad。VEGF-A165(1×1010病毒颗粒,n=18)或车辆(n=18)，输送到子宫动脉的外表面，在怀孕中期。怀孕了,随意馈送的控件仅接收车辆(n=10)。足月和出生后5个月评估后代脑重量和脑损伤的组织学指标。在学期，母体营养限制降低了胎儿脑重量，增加了所有脑区的小胶质细胞分化，但没有改变细胞死亡指数。星形胶质增生或髓鞘形成。广告。VEGF-A165增加了营养受限大坝胎儿的脑重量并减少了小胶质细胞分化。在成年后代中，母体营养限制不会改变脑重量或脑损伤的标志物，而Ad。VEGF-A165增加了海马和丘脑中的小胶质细胞分化和星形胶质细胞增生,分别。广告。VEGF-A165不影响胎儿或后代大脑中的细胞死亡或髓鞘形成。广告。VEGF-A165使暴露于母体营养限制的豚鼠胎儿的脑生长和脑损伤标志物正常化，并且可能是改善FGR并发妊娠的儿童神经发育结局的潜在干预措施。
