VEGF-mediated inflammation precedes angiogenesis in adult brain
VEGF-mediated inflammation precedes angiogenesis in adult brain
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DOI：
10.1016/j.expneurol.2004.02.010
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Wiegand, SJ
中科院分区：
文献类型：
--
作者：
Croll, SD;Ransohoff, RM;Wiegand, SJ
血管内皮细胞生长因子(VEGF)在成年大鼠脑组织中持续输注可诱导血管生成。此外，已有研究表明，血管内皮生长因子可增强脑血管通透性。成年大鼠将小鼠血管内皮细胞生长因子持续注入新皮质7天。我们研究了血管内皮生长因子诱导的大鼠新皮质血管形成的发展，并利用免疫组织化学和Western印迹分析评估了各种炎症和血管渗漏标志物的时间表达与血管生成反应的关系。我们在此报道，血管内皮生长因子介导的脑内炎症以ICAM-1和趋化因子MIP-1α上调以及单核细胞优先外渗为特征。血管内皮生长因子导致血脑屏障的戏剧性破坏，其特征是星形胶质细胞终足的血管系统投资减少。相反，血管周围的细胞在新形成的脑血管系统周围增加。此外，血脑屏障的破坏、白细胞外渗和细胞外基质沉积发生在血管增殖之前。此外，给予低剂量的血管内皮生长因子可引起通透性和炎症，而不会引起明显的血管增殖。(C)2004 Elsevier Inc.保留所有权利。
Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis when infused continuously into adult rat brain tissue. In addition, VEGF has been shown to enhance permeability in brain vasculature. Adult rats were continuously infused with mouse VEGF into neocortex for up to 7 days. We studied the development of VEGF-induced vasculature in rat neocortex and evaluated the temporal expression of a wide variety of markers for inflammation and vascular leak in relation to the angiogenic response using immunohistochemistry and Western blot analysis. We report here that VEGF-mediated inflammation in brain is characterized by upregulation of ICAM-1 and the chemokine MIP-1alpha, as well as a preferential extravasation of monocytes. VEGF causes a dramatic breakdown of the blood-brain barrier, which is characterized by decreased investment of the vasculature with astroglial endfeet. Perivascular cells, in contrast, increase around the newly formed cerebrovasculature. In addition, breakdown of the blood-brain barrier, leukocyte extravasation, and extracellular matrix deposition occur before vascular proliferation. Furthermore, administration of low doses of VEGF induces permeability and inflammation without appreciable vascular proliferation. (C) 2004 Elsevier Inc. All rights reserved.