ACUTE EXACERBATIONS OF MULTIPLE SCLEROSIS

多发性硬化症急性加重

• 批准号: 6305709
• 负责人: SUBRAMANIAM SRIRAM
• 金额: $ 0.06万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6305709
• 关键词: antiinflammatory agents; blood brain barrier; cell adhesion; clinical research; clinical trial phase I; human subject; human therapy evaluation; lymphocyte; multiple sclerosis; nervous system disorder chemotherapy; vascular endothelium

Multiple sclerosis is a chronic disease characterized by recurrent attacks of neurologyc dysfunction, due to lesions in the whate matter of the center nervous system. MS lesions evolve over time. "Active" lesions contain inflammatory cells such as lumphocytes, plasma cells, and macrophages in areas of demyelination, with evidence of phagocytosis of myelin and its breakdown products by macrophages. In contrast "inactive" lesions are hypocellular with scarring and loss of oligodendrocytes, the cells that produce myein. The presence of leukobytes in the CNS, where thay are normally absent, together with their early association with the demyelinating process, suggests that inflammation is involved in the pathogenesis of MS. Although the cause of MS is unknown, data from the published literature support immunologic or infectious factors leading to the state of chronic CNS inflammation. Migration of lymphocytes across the blood brain barrier and development of CNS inflammation is a hallmark of acute symptoms of multiple sclerosis. We will test the hypotheses that agents which interfere with the migration of cell by preventing adhesion of lymphocytes to capillary endothelium of the brain, will retard the inflammatory process and reduce or prevent the development of neurologic symptoms.

多发性硬化症是一种慢性疾病，其特征是中枢神经系统白质病变引起的神经功能障碍的反复发作。多发性硬化症的病变会随着时间的推移而发展。“活动性”病变包含炎性细胞，如脱髓鞘区域的肿块细胞、浆细胞和巨噬细胞，具有巨噬细胞吞噬髓磷脂及其分解产物的证据。相反，“非活动性”病变是细胞减少，伴有瘢痕形成和少突胶质细胞的丧失，少突胶质细胞是产生myin的细胞。通常不存在的中枢神经系统中存在白细胞，再加上它们与脱髓鞘过程的早期关联，表明炎症参与了MS的发病机制，尽管MS的病因尚不清楚，但已发表的文献数据支持免疫或感染因素导致慢性中枢神经系统炎症状态。淋巴细胞跨越血脑屏障的迁移和中枢神经系统炎症的发展是多发性硬化症急性症状的标志。我们将测试通过阻止淋巴细胞粘附到脑毛细血管内皮而干扰细胞迁移的药物，将延缓炎症过程，减少或预防神经系统症状的发展。