VEGF AND FLT - EXPRESSION TIME KINETICS IN RAT-BRAIN INFARCT

Background and Purpose Vascular endothelial growth-vascular permeabili ty factor (VEGF) is a candidate for an angiogenic and hyperpermeabilit y inducing factor in an infarct because it is a secretable mitogen spe cific for endothelial cells and is upregulated by hypoxia. Our study a ttempts to clarify the chronological expression of VEGF and its recept or (fit) system in experimental cerebral infarction. Methods With the use of a reproducible middle cerebral artery occlusion model in rats, VEGF expression was identified by Western blotting with anti-VEGF anti body. The chronological expression of the VEGF/flt system was analyzed semiquantitatively by immunohistochemical means in infarcts with diff erent time courses from 3 hours to 3 weeks. Results VEGF and fit were expressed exclusively in the ischemic brain. The bands obtained on the immunoblot at 38 and 45 kD are related td those of VEGF(121) and VEGF (165) isoforms. Macrophages, neurons, and glial cells chronologically expressed VEGF immunoreactivity in a different fashion. Both VEGF (bou nd) and fit were detected in endothelial cells along with the developm ent of angiogenesis. Conclusions In the ischemic brain the macrophages , neurons, and glial cells appear to contain VEGF. The VEGF receptor f it was induced in endothelial cells along with the progression of angi ogenesis in infarct. The VEGF/flt system is thus considered to be invo lved in the healing process of brain infarct.