Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions.

Fresh lesions in the brain and spinal cord of patients with multiple sclerosis who died shortly after the onset of symptoms were examined immunocytochemically for myelin and oligodendrocyte antigens that are known to be sequentially expressed during normal development. Cells with oligodendrocyte-like morphology that appear in large numbers throughout fresh lesions after acute myelin breakdown and before new myelin formation were found to express galactocerebroside, carbonic anhydrase, and 2',3'-cyclic nucleotide 3'-phosphohydrolase but not myelin-associated glycoprotein or myelin basic protein. They also exhibit intense surface reactivity for a carbohydrate epitope associated with the family of cell adhesion molecules recognized by the monoclonal antibody HNK-1. With the onset of remyelination and the appearance of myelin-associated glycoprotein, myelin basic proteins, CNP, and the HNK-1 epitope is newly formed myelin sheaths, perikaryon CNP and HNK-1 reactivity diminished. A possible oligodendrocyte precursor cell in the form of a large HNK-1 positive glial fibrillary acidic protein negative glial cell was observed among interfascicular oligodendrocytes in white matter bordering these hypercellular plaques. Because a similar progression in the expression of CNP and the HNK-1 epitope occurs during normal oligodendrocyte differentiation, these observations are additional evidence that extensive oligodendrocyte regeneration occurs in some plaques early in the course of the disease. The finding of large numbers of immature oligodendrocytes, presumably expressing many developmentally restricted antigens not normally present in the mature nervous system, in plaques at a particular stage in their evolution may be important in understanding why remyelination eventually fails in multiple sclerosis.