The demonstration of recurrent demyelination and remyelination of axons in the central nervous system.

A model for studying recurrent demyelination and remyelination in the central nervous system was developed by means of repeated administration of Cuprizone to mice. In contrast to the demyelination seen during the first course of Cuprizone, the recurrent demyelination was markedly protracted, displayed features of a "dying-back" gliopathy, and resulted in a greatly reduced inflammatory and glial reaction. The repeat remyelination also occurred at a slower tempo, varied markedly in completeness, and was associated with a diminished regeneration of oligodendrocytes. These results demonstrated that axons of the central nervous system in this model can be recurrently remyelinated if oligodendrocytes are available, that regeneration of oligodendrocytes is dependent upon the tissue reaction to demyelination, and that remyelinated axons are not more susceptible to demyelination than normal ones.