Animal models of demyelination

Abstract

Demyelination is a pathological feature that is characteristic of many diseases of the central nervous system (CNS) including multiple sclerosis (MS), sub-acute sclerosing panencephalomyelitis (SSPE), metachromatic leukodystrophy and Pelizaeus-Merzbacher disease. While demyelination is a pathological end-point that is common to all of these diseases, the cellular and molecular mechanisms responsible for this pathology are very different . These range from genetic defects that affect lipid metabolism in the leukodystrophies, cytopathic effects of viral infection in SSPE to the action of immunological effector mechanisms in MS and the viral encephalopathies. Irrespective of the initial cause of myelin degradation, many of these disorders are associated with some degree of CNS inflammation, as indicated by the local activation of microglia, recruitment of macrophages or the intrathecal synthesis of immunoglobulin. Many of these phenomena are now being duplicated in animal models, providing not only new insights into the pathogenesis of human demyelinating diseases , but also unexpected interrelationships between the immune response in the CNS and the pathogenesis of diseases such as Alzheimers disease and HIV encephalopathy. Autoimmune mediated models of inflammatory demyelinating CNS disease have proved particularly valuable in this respect as they allow the effects of defined immune effector mechanisms to be studied in the absence of CNS infection.