The endothelial cells which line blood vessels provide a barrier which limits the exchange of molecules across the capillary wall. Damage to the capillary endothelium can cause pathological alterations in the brain. Comparatively little is known about the molecular composition of endothelial cell membranes and their alterations in disease. Preliminary studies with a monoclonal antibody that reacts with rat central and peripheral nervous system endothelial cell membranes indicate that, in Lewis rats with experimental allergic encephalomyelitis, the antibody recognizes a pre-inflammatory, endothelial cell-specific alteration that persists during inflammation. We have proposed studies which would determine: 1) If the loss of endothelial cell reacitivity seen with the monoclonal antibody is specific for autoimmune diseases; 2) If the changes in reactivity occur in other pathological conditions where there is breakdown of the blood brain barrier; 3) When, in pre-clinical stages of autoimmune disease, do these changes first occur and what is the correlation with other known vascular changes; 4) When does reactivity with the antibody reappear in recovered animals; 5) If presentation of antigen to T cells be demonstrated in blood vessels that have lost the ability to react with the antibody; and 6) What is the antigen recognized. With these studies and future studies with other monoclonal antibodies to blood brain barrier components, we hope to contribute to the understanding of the composition of endothelial cell membranes and its relationship to pathogenesis in diseases such as multiple sclerosis. Advances in understanding of capillary function may lead to new approaches to treatment.
| Zhang, H; Sternberger, N H; Rubinstein, L J et al. (1989) Abnormal processing of multiple proteins in Alzheimer disease. Proc Natl Acad Sci U S A 86:8045-9 |
| Sternberger, L A; Zhang, H; Rubinstein, L J et al. (1989) Multiple proteins are abnormally processed in Alzheimer disease. Prog Clin Biol Res 317:763-8 |
| Poltorak, M; Freed, W J; Sternberger, L A et al. (1988) A comparison of intraventricular and intraparenchymal cerebellar allografts in rat brain: evidence for normal phosphorylation of neurofilaments. J Neuroimmunol 20:63-72 |
| Sternberger, N H; Sternberger, L A (1987) Blood-brain barrier protein recognized by monoclonal antibody. Proc Natl Acad Sci U S A 84:8169-73 |
