Progressive Expression of Vascular Endothelial Growth Factor (VEGF) and Angiogenesis After Chronic Ischemic Hypoperfusion in Rat

Cerebrovascular stenosis caused by arteriosclerosis induces failure of the cerebral circulation. Even if chronic cerebral hypoperfusion does not induce acute neuronal cell death, cerebral hypoperfusion may be a risk factor for neurodegenerative diseases. The purpose of this study was to determine if vasodilation, expression of VEGF, and neovascularization are homeostatic signs of cerebral circulation failure after permanent common carotid artery occlusion (CCAO) in the rat. Neuronal cell death in neocortex was observed 2 weeks after CCAO and gradually increased in a time-dependent manner. The diameter of capillaries and expression of VEGF also increased progressively after CCAO. Moreover, we observed unusual irregular angiogenic vasculature at 4 weeks. In conclusion, chronic hypoperfusion results in mechanisms to compensate for insufficiency in blood flow including vasodilation, VEGF expression, and neovascularization in the ischemic region. These results suggest that angiogenesis might be induced in adult brain through the support of growth factors and transplantation of vascular progenitor cells, and that neovascularization might be a therapeutic strategy for children and adults with diseases such as vascular dementia.