VEGF expression and microvascular responses to severe transient hypoxia in the fetal sheep brain
VEGF expression and microvascular responses to severe transient hypoxia in the fetal sheep brain
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DOI：
10.1038/pr.2012.191
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Walker, David W.
中科院分区：
文献类型：
--
作者：
Baburamani, Ana A.;Castillo-Melendez, Margie;Walker, David W.
背景：胎儿缺氧在永久性围产期脑损伤的发病机制中起重要作用。我们假设，缺氧诱导的脑血管生成和微血管的变化会发生在胎羊受到严重的缺氧损伤所产生的脐带闭塞（UCO）为10分钟。方法：在124-126天的妊娠期，单胎羊进行手术植入导管和放置一个可充气的袖口周围的脐带。在孕130 d诱导10 min UCO或假UCO（n = 5）。分别于UCO后24 h（n = 5）和48 h（n = 4）取胎脑，免疫组化法检测VEGF、Ki 67和血清albumin.Results：UCO后48 h，脑室下区、脑室周围和皮质下白色物质、胼胝体和皮质中VEGF表达的血管百分比增加。血管通透性的改变（白蛋白外渗）只观察到在脑室周围和皮质下的白色物质和脑室下区以下UCO.CONCLUSION：VEGF表达的上调和血浆蛋白的泄漏增加在胎羊脑中表明，微血管在白色物质是敏感的缺氧在近期的大脑。
BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.