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

开发针对 VEGF 的新型分子靶向疗法治疗脑水肿

• 批准号: 16390410
• 负责人: KOHMURA Eiji
• 金额: $ 8.38万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390410/
• 关键词: brain edema; VEGF; cold injury; ischemia

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.

在大鼠冷损伤模型中，VEGF受体拮抗剂VGA 1155显著降低脑含水量，并且在损伤后30分钟给予时获得最大效果。这种作用呈剂量依赖性，25 mg/kg剂量显示最大作用。在此剂量下，VGA 1155还显著降低了血管通透性。脑损伤的组织学评估显示，损伤后1周，VGA 1155损伤面积没有显著减少。结果提示，VGA 1155可能在冷损伤后急性期具有抗水肿作用，在线栓法造成的大鼠大脑中动脉短暂性闭塞模型中，腹腔注射VGA 1155可显著降低脑缺血后24 h的脑含水量，10 mg/kg剂量对脑含水量的影响最大。在该剂量下，通过静脉注射伊文思蓝，VGA 1155还在再灌注后4小时降低血管通透性。此外，在缺血性损伤后1周，给予VGA 1155显著减少了梗死体积并改善了神经评分。提示VGA 1155可能在短暂性局灶性脑缺血急性期具有抗水肿作用。

项目成果

Carotid artery occlusion and collateral circulation in C57Black/6J mice detected by synchrotron radiation microangiography

同步辐射显微血管造影检测C57Black/6J小鼠颈动脉闭塞及侧支循环

• 发表时间: 2006
• 期刊: Kobe J. Med. Sci. 52(5)
• 作者: M. Tamaki;K. Kidoguchi;K. Umetani
• 通讯作者: K. Umetani

Effect of VEGF receptor antagcnist (VGA1155) on brain edema in the rat cold injury model.

VEGF受体拮抗剂(VGA1155)对大鼠冷损伤模型脑水肿的影响。

• 发表时间: 2007
• 期刊: Kobe Journal of Medical Science 53(In press)
• 作者: Nakagawa A;Sato J;Hirano T;Ohki T;Saito T;Takayama K;Tominaga T.;Koyama J
• 通讯作者: Koyama J

Effect of VEGF Receptor Antagonist (VGA1155) on Brain Edema in the Rat Cold Injury Model.

VEGF 受体拮抗剂 (VGA1155) 对大鼠冷损伤模型脑水肿的影响。

• 发表时间: 2007
• 期刊: Kobe J Med Sci. 53
• 作者: Koyama J;Miyake S;Sasavama T;Kondoh T;Kohmura E.
• 通讯作者: Kohmura E.

Quantification of distension in rat cerebral perforating arteries

大鼠脑穿支动脉扩张的量化

• 发表时间: 2006
• 期刊: Neuroreport 17(14)
• 作者: Morishita A;Kondoh T;Sakurai T;Ikeda M;Bhattacharjee AK;Nakajima S;Kohmura E;Yokono K;Umetani K.
• 通讯作者: Umetani K.

In vivo X-ray angiography in the mouse brain using synchrotron radiation

• DOI: 10.1161/01.str.0000226904.96059.a6
• 发表时间: 2006-07-01
• 期刊: STROKE
• 影响因子: 8.3
• 作者: Kidoguchi, Keiji;Tamaki, Masahiro;Umetani, Keiji
• 通讯作者: Umetani, Keiji