VEGF overexpression improves mice cognitive abilities after unilateral common carotid artery occlusion

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.