In this project we study the conditions, which allow various cells of the immune system to enter the central nervous system. This involves studies on the trafficking of prelabelled T-cells through the blood brain barrier and the role of adhesion molecules and chemokines in this process.
In this project we try to define in various experimental models of autoimmune encephalomyelitis the mechanisms which lead to demyelination and axonal destruction in inflammatory demyelinating lesions. These studies show that the mechanisms of demyelination are diverse, depending upon the experimental models studied. Major factors in inducing demyelination are cytotoxic T-cells, specific auto-antibodies and products of activated macrophages.
In studying a large number of human brain biopsies and autopsies of MS patients with actively demyelinating lesions we were able to define distinctly different patterns of demyelination. These data suggest that the pathogenesis of lesions in multiple sclerosis is heterogenous between different patients and/or at different stages of disease evolution. Currently we attempt to define the exact pathogenetic mechanisms by comparing these lesional patterns with those found in defined experimental models or other human disease with defined etiology. Furthermore we are in the process of defining clinical and paraclinical markers that allow to differentiate these different patterns of pathogenesis in MS patients during their evolution of the disease. In another major research project we aim to define in detail the immunopathology of progressive MS and the relation between inflammation and neurodegeneration in this disease.
This project focuses on the role of inflammation and microglia activation in Alzheimer?s disease. This is done in parallel in experimental models and in humans. To address the question, whether chronic microglia activation in the human cortex has an effect on the formation or clearance of Alzheimer pathology, we studied neurofibrillary tangels and amyloid plaques in chronically inflamed multiple sclerosis brain. Our results show, that the basic cortical pathology of multiple sclerosis has no influence on the development of Alzheimer type pathology in the brain.
