Post-ischemic Administration of Vascular Endothelial Growth Factor Inhibitor in a Rat Model of Cerebral Venous Infarction
Post-ischemic Administration of Vascular Endothelial Growth Factor Inhibitor in a Rat Model of Cerebral Venous Infarction
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DOI：
10.2176/nmc.53.135
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发表时间：
2013-03-01
影响因子：
1.9
通讯作者：
Nakase, Hiroyuki
中科院分区：
文献类型：
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作者：
Miyake, Hitoshi;Nakagawa, Ichiro;Nakase, Hiroyuki
脑静脉缺血可导致严重的脑水肿。通过中和抗体抑制血管内皮生长因子（VEGF）活性可以完全阻断缺氧诱导的血管通透性增加。VEGF不仅可以诱导血管生成，还可以作为血管通透性（VP）因子。我们之前的研究表明，抑制VEGF可减轻急性期的VP和脑静脉梗死（CVI）。本研究探讨了抑制VEGF降低大鼠双静脉闭塞（2-VO）模型CVI的治疗时间窗。通过光化学方法闭塞相邻的皮质静脉，建立2-VO模型。雄性Wistar大鼠（n = 42）分为四组：第一组在2-VO后24小时使用VEGF拮抗剂（n = 11）；2组在2- vo后24小时用磷酸盐缓冲溶液（PBS）处理（n = 11）；第3组在2-VO后48小时给予VEGF拮抗剂治疗（n = 10）；第4组在2-VO后48小时用PBS治疗（n = 10）。2-VO后7天进行组织学检查。第1组CVI面积明显小于第2、3、4组(p
Cerebral venous ischemia can result in severe brain edema. Inhibition of vascular endothelial growth factor (VEGF) activity by a neutralizing antibody can completely block the hypoxia-induced increase in vascular permeability. VEGF, which induces angiogenesis, also acts as a vascular permeability (VP) factor. We previously showed that inhibition of VEGF attenuates VP and reduces cerebral venous infarction (CVI) in the acute stage. The present study investigated the therapeutic time window during which inhibition of VEGF can reduce CVI in a rat two-vein occlusion (2-VO) model. A 2-VO model was created by photochemically occluding two adjacent cortical veins. Male Wistar rats (n = 42) were assigned to one of four groups: Group 1 was treated with a VEGF antagonist at 24 hours after 2-VO (n = 11); Group 2 was treated with phosphate-buffered solution (PBS) at 24 hours after 2-VO (n = 11); Group 3 was treated with a VEGF antagonist at 48 hours after 2-VO (n = 10); and Group 4 was treated with PBS at 48 hours after 2-VO (n = 10). The developing ischemic infarct was evaluated histologically at 7 days after 2-VO. CVI areas were significantly smaller in Group 1 than in Groups 2, 3, and 4 (p