THE NORTON-LECTURE - A REVIEW OF THE OLIGODENDROCYTE IN THE MULTIPLE-SCLEROSIS LESION

The mechanisms involved in the elimination of oligodendrocytes and mye lin from the demyelinated plaque of multiple sclerosis (MS) are inextr icably intertwined and yet most investigations tend to consider them s eparately. This short review revisits the problem of oligodendrocyte p athology in MS and attempts to put the topic into perspective by exami ning the numerous immunologically-active molecules associated with the oligodendrocyte, some, but not all, cross-reactive with myelin. The c onsensus of opinion is that myelin is the primary target in MS but tha t oligodendrocytes are eventually lost from the lesion. Reappraisal of recent and past works brings into focus a possible key role for solub le mediators, in particular antibody and the pro-inflammatory cytokine , TNF alpha, in oligodendrocyte loss and myelin in MS. Despite extensi ve neuropathologic investigation by a number of laboratories, no evide nce has yet been found to support the concept that apoptosis might acc ount for oligodendrocyte depletion in MS, even though molecules belong ing to the apoptotic cascade can be expressed by oligodendrocytes in a nd around lesions. indeed, abundant evidence has been presented to sho w 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 even tually lost, probably via a cytolytic pathway. Strategies to block the progression of CNS inflammation in EAE and MS appear to promote the s urvival of oligodendrocytes and to enhance remyelination. Such strateg ies appear to hold much promise for the MS patient. (C) 1997 Elsevier Science B.V.