The transvascular migration of lymphocytes and other leukocytes from blood to the central nervous system (CNS) is characteristic of many CNS disorders such as stroke, multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). The emigration of cells into peripheral tissues is preceded by adhesive interactions utilizing specific molecules (e.g., integrins) on the surface of leukocytes and endothelial cells (EC). Such adhesive interactions could also lead to local vessel occlusion and circulatory impairment resulting in circumscribed ischemia or hemorrhagic tissue damage characteristic of disorders such as atherosclerosis and stroke. These experiments demonstrate the expression of intercellular adhesion molecule-1 (ICAM-1) on cerebrovascular EC which constitute the blood-brain barrier (BBB). In addition to ICAM-1, other molecules were observed using monoclonal antibodies (mAb) prepared from rats inoculated with cerebrovascular EC. The results also show that ICAM expression by cerebrovascular EC can be modulated by cytokines (i.e., tumor necrosis factor-alpha,[TNF]; interleukin-1[IL-1]; interferon-gamma, [IFN]; and transforming growth factor-beta, [TGF] which have clinical relevance to all the above- mentioned disorders. The results indicate that adhesion molecule expression by EC at the site of the BBB may play a pathologic role (i.e.,leukocyte adhesion and/or transmigration) in a wide range of CNS disorders including stroke, MS, and EAE.
