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

在大鼠冷损伤模型中，VEGF受体拮抗剂VGA1155显著降低脑含水量，且在损伤后30分钟给药效果最大。该效应呈剂量依赖性，剂量为25 mg/kg时效果最大。在此剂量下，VGA1155也显著降低了血管通透性。脑损伤组织学评价显示，VGA1155损伤后1周，脑损伤面积无明显减少。提示VGA1155在冻伤后急性期可能具有消肿作用。在大鼠大脑中动脉短暂性闭塞模型中，缝合闭塞2小时后，脑缺血后24小时，腹腔注射VGA1155可显著降低脑含水量，以10 mg/kg剂量对脑含水量影响最大。在此剂量下，静脉注射Evans蓝再灌注后4小时，VGA1155也能降低血管通透性。此外，在缺血损伤后1周，给药VGA1155可显著减少梗死面积并改善神经学评分。提示VGA1155可能在短暂局灶性脑缺血急性期有抗水肿作用。

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.