VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia.
VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia.
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DOI：
10.1172/jci17977
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发表时间：
2003-06
期刊：
影响因子：
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通讯作者：
Yunjuan Sun;K. Jin;Lin Xie;Jocelyn T Childs;X. Mao;A. Logvinova;D. Greenberg
中科院分区：
文献类型：
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作者：
Yunjuan Sun;K. Jin;Lin Xie;Jocelyn T Childs;X. Mao;A. Logvinova;D. Greenberg
血管内皮生长因子（VEGF）是一种血管生成蛋白，在缺血性疾病（包括卒中）中具有治疗潜力。VEGF赋予神经保护作用，促进神经发生和脑血管生成，但这些作用在缺血性脑中可能相互作用的方式知之甚少。我们制作局灶性脑缺血大脑中动脉闭塞90分钟，在成年大鼠大脑和测量梗死面积，神经功能，BrdU标记的神经增殖区，和vWF免疫反应血管配置文件，没有和脑室内管理VEGF再灌注1-3天。VEGF减少梗死面积，改善神经功能，增强齿状回和脑室下区新生神经元的延迟存活，刺激纹状体缺血半暗带的血管生成，但不包括齿状回。我们的结论是，在缺血性脑血管内皮生长因子发挥急性神经保护作用，以及较长的潜伏期的新神经元的存活和血管生成的影响，这些影响似乎独立运作。因此，VEGF可能通过多种机制改善卒中的组织学和功能结局。
Vascular endothelial growth factor (VEGF) is an angiogenic protein with therapeutic potential in ischemic disorders, including stroke. VEGF confers neuroprotection and promotes neurogenesis and cerebral angiogenesis, but the manner in which these effects may interact in the ischemic brain is poorly understood. We produced focal cerebral ischemia by middle cerebral artery occlusion for 90 minutes in the adult rat brain and measured infarct size, neurological function, BrdU labeling of neuroproliferative zones, and vWF-immunoreactive vascular profiles, without and with intracerebroventricular administration of VEGF on days 1-3 of reperfusion. VEGF reduced infarct size, improved neurological performance, enhanced the delayed survival of newborn neurons in the dentate gyrus and subventricular zone, and stimulated angiogenesis in the striatal ischemic penumbra, but not the dentate gyrus. We conclude that in the ischemic brain VEGF exerts an acute neuroprotective effect, as well as longer latency effects on survival of new neurons and on angiogenesis, and that these effects appear to operate independently. VEGF may, therefore, improve histological and functional outcome from stroke through multiple mechanisms.