The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Australia.
Pediatr Res. 2013 Mar;73(3):310-6. doi: 10.1038/pr.2012.191. Epub 2012 Dec 10.
Fetal hypoxia contributes significantly to the pathogenesis of permanent perinatal brain injury. We hypothesized that hypoxia-induced cerebral angiogenesis and microvascular changes would occur in fetal sheep subjected to a severe hypoxic insult produced by umbilical cord occlusion (UCO) for 10 min.
At 124-126 d of gestation, singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. A 10-min UCO or sham UCO (n = 5) was induced at 130 d gestation. The fetal brain was collected at 24 h (n = 5) or 48 h (n = 4) after UCO for immunohistochemical analysis of vascular endothelial growth factor (VEGF), Ki67, and serum albumin.
By 48 h after UCO, the percentage of blood vessels expressing VEGF had increased in the subventricular zone, periventricular and subcortical white matter, corpus callosum, and cortex. Alterations in vascular permeability (albumin extravasation) were observed only in the periventricular and subcortical white matter and the subventricular zone following UCO.
The upregulation of VEGF expression and increased leakage of plasma protein in the fetal sheep brain show that the microvasculature in white matter is sensitive to hypoxia in the near-term brain.
胎儿缺氧是永久性围产期脑损伤发病机制的重要原因。我们假设，在 10 分钟的脐带结扎（UCO）引起的严重缺氧刺激下，胎儿羊会发生缺氧诱导的大脑血管生成和微血管变化。
在妊娠 124-126 天时，单胎胎儿羊接受了导管植入和脐带周围可充气袖带放置的手术。在妊娠 130 天时，对胎儿羊进行了 10 分钟的 UCO 或假手术 UCO（n = 5）。在 UCO 后 24 小时（n = 5）或 48 小时（n = 4）收集胎儿大脑，用于血管内皮生长因子（VEGF）、Ki67 和血清白蛋白的免疫组织化学分析。
在 UCO 后 48 小时，血管内皮生长因子（VEGF）表达的血管百分比在侧脑室下区、脑室周围和皮质下白质、胼胝体和皮质中增加。只有在 UCO 后，脑室周围和皮质下白质以及侧脑室下区才观察到血管通透性改变（白蛋白外渗）。
在近足月脑，VEGF 表达上调和血浆蛋白渗漏增加表明白质微血管对缺氧敏感。
