Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats
Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats
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DOI：
10.1093/jnen/61.10.914
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发表时间：
2002-10-01
影响因子：
3.2
通讯作者：
Merrill, MJ
中科院分区：
文献类型：
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作者：
Proescholdt, MA;Jacobson, S;Merrill, MJ
多发性硬化（MS）的活动性病变的特征是血脑屏障（BBB）的破坏，毛细血管内皮细胞上粘附分子的上调和血管周围炎症。血管内皮生长因子（VEGF）介导血管生理学的多个方面，包括调节。为了研究VEGF表达和CNS自身免疫性疾病之间的可能关系，我们通过免疫组织化学和原位杂交检测了与正常白色物质相比，MS斑块中VEGF的表达。VEGF表达在急性和慢性MS斑块中一致上调。我们还检测了VEGF在大鼠实验性变态反应性脑脊髓炎（EAE）过程中的表达，在EAE的发展过程中，VEGF阳性细胞在脊髓中增加，具有星形胶质细胞形态，并被发现与炎性细胞相关。此外，脑内输注血管内皮生长因子在动物先前免疫与髓鞘碱性蛋白诱导炎症反应的大脑。而在未处理动物中输注载体或输注VEGF则没有。这些结果表明，VEGF的过度表达可能会加剧炎症反应的自身免疫性疾病的中枢神经系统诱导，局灶性血脑屏障的破坏和迁移的炎性细胞进入病变。
The active lesions in multiple sclerosis (MS) are characterized by blood-brain-harrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation. suggesting that altered vessel permeability and activated endothelial Celts are involved in the pathogenesis of the disease, Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter by immunohistochemistry and in situ hybridization. VEGF expression was consistently upregulated in both acute and chronic MS plaques. We also examined VEGF expression during the Course of experimental allergic encephalomyelitis (EAE) in rats, VEGF-positive cells with astrocytic morphology increased in the spinal cord during the development of EAE and were found in association with inflammatory Cells. Furthermore, intracerebral infusion of VEGF in animals previously immunized with myelin basic protein induced an inflammatory response in the brain. whereas infusion of vehicle, or infusion of VEGF in naive animals, did not. These results suggest that overexpression of VEGF may exacerbate the inflammatory response in autoimmune diseases of the CNS by inducing, focal BBB breakdown and migration of inflammatory cells into the lesions.