Establishment of selective VEGF inhibition treatment as a novel therapeutic strategy against ischemic stroke

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Vascular endothelial growth factor(VEGF), might be associated with the blood-brain barrier(BBB) disruption after focal cerebral ischemia : however, it remains unknown whether hemorrhagic transformation(HT) after tissue plasminogen activator(tPA) treatment is related to the activation of VEGF signaling pathway in BBB. Here, we hypothesized that inhibition of VEGF signaling pathway can attenuate HT after tPA treatment. Rats subjected to thromboembolic focal cerebral ischemia were assigned to groups treated with tPA at 1 h or 4 h after ischemia. Anti-VEGF neutralizing antibody or control antibody was administered simultaneously with tPA. At 24 h after ischemia, we evaluated the effects of the antibody on the VEGF signal cascades and HT. Delayed tPA treatment at 4 h after ischemia promoted VEGF signal activation and HT. Combination treatment with tPA and the anti-VEGF neutralizing antibody significantly attenuated these changes. Inhibition of VEGF signaling pathway may be a promising therapeutic strategy for attenuating HT after tPA treatment.