Demyelinating diseases and neuroinflammation

Abstract

Demyelination is a neuropathological condition of the nervous system, where the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected neurons. Several central nervous system (CNS) demyelinating disorders have been described in humans including, multiple sclerosis (MS), neuromyelitis optica (Devic’s disease), acute disseminated encephalomyelitis, and osmotic demyelination (central pontine myelinolysis, extrapontine myelinolysis). The primary cellular target in demyelination pathology is believed to be myelin itself or the myelin-forming cells, oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS). The mechanisms of demyelinating diseases are essentially unknown. It has been apparent in several current studies that demyelination/axonal loss occurs mainly by inflammation composed predominantly of lymphocytes and monocytes/macrophages. However, evidences suggest that demyelination/axonal loss may not be entirely immune mediated and could be due to direct virus or toxin-induced damage. Microglia, the major resident immune cells in the CNS, are considered as the key cellular mediators of neuroinflammatory demyelinating processes. Chronic/remitting neurological disease such as MS has long been considered an inflammatory autoimmune disease with the infiltration of peripheral myelinspecific T cells into the CNS. With the rapid advancement in the field of microglia and astrocytic neurobiology, the term neuroinflammation progressively started to denote chronic CNS cell-specific inflammation in MS. The direct glial responses in MS are different from conventional peripheral immune responses. The presence of activated microglia in the chronic active inflammatory demyelinating lesions is the foundation of neuroinflammatory pathology of demyelination.