Blood Vascular Changes Associated with Chronic Active Multiple Sclerosis Plaques: Detection by Anti-Human Brain Vascular Endothelia-Specific Monoclonal Antibodies
Michael O. Ibiwoye, Christian Clement, Joseph O. Olubadewo, Alberto E. Musto, Timothy A. Foster, John C. Broome, Daniel Crooks

Abstract
Recent studies suggest that brain angiogenesis is an important component of multiple sclerosis (MS) lesions and may be a potential target for investigating the pathogenesis and treatment of the disease. In this preliminary study, a panel of blood vessel-specific mouse monoclonal antibodies raised against normal human whole temporal lobe homogenates was used to study changes in vascular immunoreactivity and morphological features in cerebral tissue obtained from two clinically and neuropath logically confirmed cases of chronic active multiple sclerosis. Immunoperoxidase and immunofluorescence staining techniques revealed more frequent detection of intensely labelled blood vessels within active multiple sclerosis plaques compared to the adjacent white matter and normal control brain sections. Strongly reactive vascular endothelial sprouts as detected by epifluorescence immunohistochemistry were observed in whole vessel mounts isolated by partial homogenization and sieving of cerebral tissue containing active plaques, but not in vessels isolated from normal control cerebral tissue. These vascular changes suggest increased angiogenesis and endothelial proliferation within the active multiple sclerosis plaques and may be part of the inflammatory response by the central nervous system to this disease. This study also suggests that monoclonal antibodies raised specifically against whole homogenates of human brain could potentially be useful tools for investigations of antigenic heterogeneity and morphologic characterization of vascular endothelial changes associated with multiple sclerosis lesions in the human model system. Plans are under way to further investigate the exact biochemical nature of the specific antigens being recognized by the individual monoclonal antibodies.

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