Mechanisms of white matter damage in multiple sclerosis

Authors

  • Hans Lassmann

    Corresponding author
    1. Center for Brain Research, Medical University of Vienna, Austria
    • Address correspondence to Dr. Hans Lassmann, Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Wien, Austria. E-mail: hans.lassmann@meduniwien.ac.at

    Search for more papers by this author

Abstract

Glia cells are mediators as well as targets of the chronic inflammatory process in the central nervous system of multiple sclerosis (MS) patients. They are involved in the control of autoimmunity, in the propagation and termination of the inflammatory reaction, in the induction of demyelination and neurodegeneration, and in remyelination and scaring. Demyelination, as well as neuronal and GLIA cell damage are induced by different immunological mechanisms including components of the adaptive and innate immune system. Oxidative injury resulting in mitochondrial dysfunction is one important mechanism of tissue injury. It is in part driven by the inflammatory response and the production of oxygen radicals mainly in microglia and macrophages. With increasing age of the patients and disease progression, oxidative injury is further amplified by additional mechanisms including central nervous system damage related microglia activation, progressive mitochondrial damage, and age-dependent iron accumulation within the human central nervous system. The inflammatory mechanisms associated with lesion formation in MS are to a large extent reflected in experimental models of inflammatory demyelination, such as autoimmune encephalomyelitis. This is not the case for the amplification mechanisms of oxidative injury, which mainly operate in the progressive stage of the disease. GLIA 2014;62:1816–1830

Ancillary