REDUCTION OF ISCHEMIC DAMAGE BY APPLICATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN RAT-BRAIN AFTER TRANSIENT ISCHEMIA

Vascular endothelial growth factor (VEGF) is a secreted polypeptide an d plays a pivotal role in angiogenesis in vivo. However, it also incre ases vascular permeability, and might exacerbate ischemic brain edema. The effect of this factor on the brain after transient ischemia was i nvestigated in terms of infarct volume and edema formation, as well as cellular injury. After 90 minutes of transient middle cerebral artery occlusion, VEGF (1.0 ng/mu L, 9 mu L) was topically applied on the su rface of the reperfused rat brain. A significant reduction of infarct volume was found in animals with VEGF application (P < 0.001) at 24 ho urs of reperfusion as compared with cases with vehicle treatment. Brai n edema was significantly reduced in VEGF-treated animals (P = 0.01), and furthermore, extravasation of Evans blue was also decreased in tho se animals (P < 0.01). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling and immunohistochemical analysis for 70-kDa heat shock protein showed an amelioration of the stainings at 24 and 48 hours after reperfusion with VEGF treatment, which indic ated reduction of neuronal damage. These results indicate that treatme nt with topical VEGF application significantly reduces ischemic brain damage, such as infarct volume, edema formation, and extravasation of Evans blue, and that the reductions were associated with that of neuro nal injury.