Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre

Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated pro found and synchronous demyelination of the corpus callosum. which was virtu ally complete by 4 weeks of exposure. Interestingly. even in the face of a continued exposure to cuprizone. there was spontaneous remyelination 2 week s later. This remyelination preferentially involved smaller calibre axons. There was a suggestion of yet another cycle of demyelination (at 10 weeks) and remyelination (at 12 weeks). but by 16 weeks of exposure. the regenerat ive capacity was exhausted and the animals were near death. The relapsing-r emitting pattern suggests this may be a useful model for certain human demy elinating disorders. In contrast to the above chronic model. the corpus cal losum from mice exposed to cuprizone for only 6 weeks continued to remyelin ate, with 67%, of the axons being myelinated or remyelinated at 10 weeks. I nterestingly, a significant reduction in the mean value for axonal diameter was observed during acute demyelination. Upon remyelination. however, the axonal calibre distribution returned to near-normal. In contrast, when mice were maintained on a cuprizone diet for 16 weeks, the mean value for axona l diameter was reduced to 60% of normal. These results provide further evid ence that the interactions between oligodendrocytes adn exons alter axonal calibre.