The effect of immunosuppressive protocols on spontaneous CNS remyelinationfollowing toxin-induced demyelination

Glial cell transplantation is a potential therapy for human demyelinating d isease, though obtaining large numbers of human myelinating cells for trans plantation remains a major stumbling block. Autologous transplantation is c urrently not possible, since the adult human CNS is not a good source of ol igodendrocyte precursors, and long-term immunosuppression of engrafted allo geneic or xenogeneic cells is therefore likely to be necessary. Immunosuppr essive drugs may need to be used in situations where more recent, active ar eas of demyelination are undergoing endogenous. remyelination. It is theref ore pertinent to establish the extent to which immunosuppressive protocols will suppress spontaneous remyelination. In order to investigate this issue , we created demyelinating lesions in the spinal cord of adult rats and com pared the extent of remyelination in animals receiving different immunosupp ressive treatments. In animals given only cyclosporin A, there was no diffe rence in the extent of either Schwann cell or oligodendrocyte. remyelinatio n of ethidium bromide-induced demyelinating lesions. However, in animals gi ven cyclophosphamide, either alone or in combination with cyclosporin, ther e was a significant reduction in the extent of oligodendrocyte-mediated rem yelination. These results demonstrate that cyclophosphamide is deleterious to oligodendrocyte remyelination and for this reason should be used with ca ution in patients with demyelinating disease. (C) 2001 Elsevier Science B.V . All rights reserved.