Plaschke Konstanze, Staub Janina, Ernst Evelyn, Marti Hugo H
Department of Anesthesiology, Medical Faculty, University of Heidelberg, Germany.
Exp Neurol. 2008 Dec;214(2):285-92. doi: 10.1016/j.expneurol.2008.08.014. Epub 2008 Sep 11.
Angiogenesis and neurogenesis are adaptive responses protecting cerebral tissue from hypoxic-ischemic injury. Both processes seem to be governed by hypoxia-induced growth factors, of which vascular endothelial growth factor (VEGF) is a prominent example. The aim of this study was to investigate the influence of VEGF overexpression (V1 mice) on mice cognitive function and cerebral structure under moderate cerebral oligemia. In 33 V1 and wild-type (wt) mice, the left common carotid artery was permanently occluded (CCAO) under acute (48 h) and subchronic (12 days) conditions. Sham operation was performed in 35 mice (controls). Psychometric testing was done using holeboard test and Morris Water Maze system, immunohistochemistry was performed for detection of cerebral apoptosis, nestin and CD31 expression. The results show that under control conditions V1 mice showed better spatial cognitive abilities as compared to their wt littermates. During CCAO, time and distance to reach a hidden platform in Water Maze were shorter in V1 mice as compared to wt animals, indicative of faster learning and better spatial memory processes. While no signs of necrosis or apoptosis were detected, immunohistochemistry showed that VEGF transgenity was related to higher number of nestin-positive precursor cells. Finally, acute CCAO was paralleled by a reduction of CD31 staining in wt but not V1 mice. We conclude that VEGF overexpression led to a protective effect on cognitive function, because V1 mice showed evidence for faster spatial learning and better memory, as well as an increased number of neuronal precursor cells and a prevention of endothelial cell loss after CCAO.
血管生成和神经发生是保护脑组织免受缺氧缺血性损伤的适应性反应。这两个过程似乎都受缺氧诱导生长因子的调控，其中血管内皮生长因子（VEGF）就是一个突出的例子。本研究的目的是探讨VEGF过表达（V1小鼠）对中度脑缺血小鼠认知功能和脑结构的影响。在33只V1小鼠和野生型（wt）小鼠中，在急性（48小时）和亚慢性（12天）条件下永久性结扎左颈总动脉（CCAO）。35只小鼠进行假手术（对照组）。使用洞板试验和Morris水迷宫系统进行心理测量测试，采用免疫组织化学法检测脑凋亡、巢蛋白和CD31表达。结果显示，在对照条件下，V1小鼠比其野生型同窝小鼠表现出更好的空间认知能力。在CCAO期间，与野生型动物相比，V1小鼠在水迷宫中到达隐藏平台的时间和距离更短，表明学习更快且空间记忆过程更好。虽然未检测到坏死或凋亡迹象，但免疫组织化学显示VEGF转基因与巢蛋白阳性前体细胞数量增加有关。最后，急性CCAO伴随着野生型小鼠而非V1小鼠CD31染色的减少。我们得出结论，VEGF过表达对认知功能产生了保护作用，因为V1小鼠表现出空间学习更快、记忆更好的证据，以及神经元前体细胞数量增加和CCAO后内皮细胞损失得到预防。
