Karlik Stephen J, Roscoe Wendi A, Patinote Cindy, Contino-Pepin Christiane
Department of Pathology, University of Western Ontario, London, Ontario, Canada, USA.
Cent Nerv Syst Agents Med Chem. 2012 Mar;12(1):7-14. doi: 10.2174/187152412800229125.
What is the origin of the complex vascular changes that exist in the CNS lesions of Multiple Sclerosis (MS)? From the beginning of the study of the pathological changes in MS in the 19th century, lesions were seen to be associated with veins. On a microscopic level, there have been numerous pathological changes to these vessels including altered structure and permeability, fibrinolysis, iron-related alterations and collagen deposition. Vascular changes in inflammatory conditions outside the CNS are well documented and we hypothesize that angiogenesis (the generation of new blood vessels from existing) is an integral process of lesion development and spread in MS. We demonstrated similar vascular abnormalities in MS and in the animal model, EAE. We measured the increase in angiogenesis-related genes in EAE and review herein the effectiveness of chemical inhibitors of angiogenesis (SU5416, thalidomide and several derivatives). We postulate that interference with angiogenesis provides a suitable non-immunological target for investigation in MS.
多发性硬化症（MS）中枢神经系统病变中存在的复杂血管变化的起源是什么？自19世纪开始研究MS的病理变化以来，病变就被发现与静脉有关。在微观层面上，这些血管发生了许多病理变化，包括结构和通透性改变、纤维蛋白溶解、铁相关改变以及胶原蛋白沉积。中枢神经系统外炎症状态下的血管变化已有充分记录，我们推测血管生成（从现有血管生成新血管）是MS病变发展和扩散的一个不可或缺的过程。我们在MS和动物模型实验性自身免疫性脑脊髓炎（EAE）中证明了类似的血管异常。我们测量了EAE中血管生成相关基因的增加，并在此回顾血管生成化学抑制剂（SU5416、沙利度胺及几种衍生物）的有效性。我们假设干扰血管生成提供了一个适合在MS中进行研究的非免疫靶点。
