Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) affecting over 2.5 million individuals worldwide. MS debuts generally between the age of 20 and 30 and is one of the most disabling neurodegenerative diseases in young adults. The pathological hallmark of MS is demyelination. Central phenomenon in MS lesion pathology is the brain macrophage that phagocytoses myelin. Subsequent blockade of conduction in naked axons and axonal damage cause the neurological deficits characteristic for MS. The cause of MS is unknown. Both genetic and environmental factors play a role. Antigen specific T and B-cell activity has been suggested to cause brain macrophages to demyelinate axons, but the antigen that triggers such immune response is currently unknown. The clinical course and the pathology strongly vary between patients. The disease may start either with a relapsing or primary progressive course. The degree of macrophage activation, demyelination, remyelination and axonal damage differs between patients.

Macrophage-Mediated Demyelination of Axons

Microglia activation in MS

In normal appearing white matter microglia cells are in a state of alertness. It is not clear what alerts the microglia cells. We postulate that a second hit fully activates these alerted microglia to start to demyelinate. The second hit may be effector T cells.