Development of a novel molecular targeting therapy against VEGF for brain edema

在大鼠冷损伤模型上，血管内皮生长因子受体拮抗剂VGA1155可显著降低脑组织含水量，以伤后30min给药效果最好。该作用呈剂量依赖性，以25 mg/kg剂量作用最强。在这个剂量下，VGA1155也显著降低了血管通透性。脑损伤组织学评估显示，VGA1155致伤后1周损伤面积无明显缩小。在线栓法造成大鼠大脑中动脉短暂性脑缺血模型上，VGA1155可显著降低脑缺血后24小时的脑组织含水量，其中以10 mg/kg剂量作用最大。在此剂量下，VGA1155还可通过静脉注射伊文思蓝降低再灌注后4小时的血管通透性。此外，在缺血损伤后1周，应用VGA1155可显著缩小脑梗塞体积并改善神经功能评分。提示VGA1155在短暂性局灶性脑缺血急性期可能具有抗水肿作用。

In the rat cold injury model, the VEGF receptor antagonist VGA1155 significantly reduced the brain water content and the maximum effect was obtained when given at 30 minutes after injury. This effect was in dose-dependent manner and the dose of 25 mg/kg showed the maximum effect. With this dose, VGA1155 also significantly reduced vascular permeability. Histological evaluation of brain lesion showed no significant reduction of damaged area 1 week after injury by VGA1155. The data suggest that VGA1155 may have antiedematous effect in acute phase after cold injury.In the rat middle cerebral artery transient occlusion model, induced by the suture occlusion method for 2 hours, the brain water content at 24 hours after cerebral ischemia was significantly reduced by intraperitoneal administration of VGA1155 and the dose of 10 mg/kg showed the maximum effect on brain water content. With this dose, VGA1155 also reduced vascular permeability at 4 hours after the reperfusion by intravenous injection of Evans blue. Furthermore, VGA1155 administration significantly reduced infarct volume and improved neurological scores at 1 week after ischemic injury. The data suggested that VGA1155 may have antiedematous effect in acute phase after transient focal cerebral ischemia.