The Norton Lecture: a review of the oligodendrocyte in the multiple sclerosis lesion.
The mechanisms involved in the elimination of oligodendrocytes and myelin from the demyelinated plaque of multiple sclerosis (MS) are inextricably intertwined and yet most investigations tend to consider them separately. This short review revisits the problem of oligodendrocyte pathology in MS and attempts to put the topic into perspective by examining the numerous immunologically-active molecules associated with the oligodendrocyte, some, but not all, cross-reactive with myelin. The consensus of opinion is that myelin is the primary target in MS but that oligodendrocytes are eventually lost from the lesion. Reappraisal of recent and past works brings into focus a possible key role for soluble mediators, in particular antibody and the pro-inflammatory cytokine, TNF alpha, in oligodendrocyte loss and myelin in MS. Despite extensive neuropathologic investigation by a number of laboratories, no evidence has yet been found to support the concept that apoptosis might account for oligodendrocyte depletion in MS, even though molecules belonging to the apoptotic cascade can be expressed by oligodendrocytes in and around lesions. Indeed, abundant evidence has been presented to show that oligodendrocytes initially respond to the demyelinating insult in MS by proliferating and elaborating new myelin but, no doubt due to the relentless progression of inflammatory events, the cells are eventually lost, probably via a cytolytic pathway. Strategies to block the progression of CNS inflammation in EAE and MS appear to promote the survival of oligodendrocytes and to enhance remyelination. Such strategies appear to hold much promise for the MS patient.
Raine
C S
CS
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461, USA. raine@aecom.yu.edu
D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009836:Oligodendroglia / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D013194:Staining and Labeling