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

血管内皮生长因子（VEGF）可能与局灶性脑缺血后血脑屏障（BBB）的破坏有关，但组织型纤溶酶原激活剂（tPA）治疗后的出血性转化（HT）是否与BBB中VEGF信号通路的激活有关尚不清楚。在这里，我们假设抑制VEGF信号通路可以减轻tPA治疗后的HT。将血栓栓塞性局灶性脑缺血大鼠分为缺血后1 h或4 h tPA治疗组。抗VEGF中和抗体或对照抗体与tPA同时施用。在缺血后24小时，我们评估了抗体对VEGF信号级联和HT的影响。缺血后4h延迟tPA处理促进VEGF信号激活和HT。tPA和抗VEGF中和抗体的联合治疗显著减弱了这些变化。抑制VEGF信号通路可能是tPA治疗后减轻HT的一种有前途的治疗策略。

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.