Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction
Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction
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DOI：
10.1161/01.str.0000165925.20413.14
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发表时间：
2005-06-01
期刊：
影响因子：
8.3
通讯作者：
Sakaki, T
中科院分区：
文献类型：
--
作者：
Kimura, R;Nakase, H;Sakaki, T
背景和目的--脑静脉缺血常导致严重的脑水肿。血管内皮生长因子(VEGF)又称血管通透性(VP)因子，可诱导血管生成。本研究旨在探讨抑制血管内皮生长因子(VEGF)能否减少大鼠2-VO模型的脑水肿形成和脑静脉梗塞(CVI)。方法：采用2-VO模型。雄性Wistar大鼠(n=25)分为两组：一组给予血管内皮生长因子拮抗剂(拮抗剂组，n=10)，另一组给予磷酸盐缓冲液(PBS组，n=15)。2-VO后即刻腹腔注射血管内皮生长因子拮抗剂或PBS。结果血管内皮生长因子仅在血管源性水肿区神经元胞浆内表达，水图表观弥散系数呈高信号区。与PBS组相比，拮抗剂组的脑缺血体积明显小于PBS组(P<；0.05)。结论：我们的研究首次提供证据表明，抑制血管内皮生长因子可以减轻急性期的VP和CVI。虽然血管内皮生长因子是一种重要的血管生成因子，但我们认为抑制血管内皮生长因子可能是治疗脑水肿和CVI的一种新方法。
Background and Purpose - Cerebral venous ischemia often induces severe brain edema. Vascular endothelial growth factor ( VEGF), which induces angiogenesis, is also known as vascular permeability (VP) factor. The present study was undertaken to investigate whether the inhibition of VEGF could reduce brain edema formation and cerebral venous infarction (CVI) in a rat 2-vein occlusion (2-VO) model.Methods - We used 2-VO model in which 2 adjacent cortical veins were photochemically occluded. Male Wistar rats ( n = 25) were divided into 2 groups: one group was treated with a VEGF antagonist ( antagonist group, n = 10) and the second group was treated with phosphate-buffered solution (PBS) ( PBS group, n = 15). VEGF antagonist or PBS was injected intraperitoneally immediately after 2-VO. The developing ischemic infarct was evaluated by magnetic resonance imaging (MRI) and histology 24 hours after occlusion.Results - VEGF expression was observed in the cytoplasm of neurons exclusively in the area of vasogenic edema that was shown as a high-intensity area in the apparent diffusion coefficient of water map. Ischemic volumes calculated from each MR images, which are related to infarction and/or vasogenic edema, respectively, were significantly smaller in the antagonist group as compared with the PBS group ( P < 0.05)Conclusions - Our study is the first to provide evidence that the inhibition of VEGF attenuates VP and reduces CVI in the acute stage. Although VEGF is a significant angiogenesis factor, we concluded that the inhibition of VEGF might be a new therapy for both brain edema formation and CVI.