9. Investigating the relationship between Fibrinogen deposition and myelomonocytic cell infiltration in EAE Spinal Cord

Abstract

Multiple sclerosis and its animal model, experimental autoimmune encephalitis (EAE), are primarily characterized by inflammatory degeneration. It has also been shown that deposition of fibrinogen from the blood in spinal cord tissue increased in MS and EAE. Fibrinogen is a substrate molecule found in the blood for a receptor called CD11 expressed on the surface of both brain and blood immune cells. Using a technique to light up specific tissue (called immunofluorescence), we demonstrate that there is a positive correlation between levels of fibrinogen deposition in spinal cord and the progression of clinical symptoms. Contrary to previous research, our past work indicated that brain immune cells play a limited role in diseaseprogression, while immune cells in the blood are critical. Thus an alternative interpretation of these results may be that blocking fibrinogen deposition within the spinal cord during EAE reduces the infiltration of blood immune cells into the spinal cord. Investigating this experimentally, however, is complicated by the inability to distinguish blood and brain resident immune cells. To circumvent this, we use parabiosisirradiation-separation models to investigate the replacement of circulating immune cells, which leads to the dynamic assessment of blood immune cell infiltration in spinal cord. We have used fibrinogen deposits during EAE, thereby successfully identifying a pathological component, and a immunofluorescence tovisualize fluorescent blood cells within spinal cord and their relationship to therapeutic target for multiple sclerosis.