Background and purpose: Heterogeneity of multiple sclerosis lesions has been recently indicated: In addition to T-cell-mediated or T-cell plus antibody-mediated autoimmune mechanisms (patterns I-II) two other patterns (IIl-IV) were described. Patterns Ill-IV are characterized by primary oligodendrocyte dystrophy, reminiscent of virus- or toxin-induced demyelination rather than autoimmunity. It was described more than 30 years ago that dietary application of a copper-chelating agent called cuprizone results in primary oligodendrocyte degeneration which is followed by demyelination. The aim of the present study was to examine the regional distribution of cuprizone induced oligodendrocyte dystrophy and demyelination in the nervous system of mice. MATERIAL A METHODS: Demyelination was induced in male weanling Swiss-Webster mice by feeding them on a diet containing 0.6% (W/W) cuprizone bis(cyclohexanone)-oxalyldihydrazone (G. F. Smith Chemical, Columbus OH) for 8 weeks. Animals were sacrificed after 3, 7, 14, 27, 35, 56 days of cuprizone administration. Samples were taken from corpus callosum, anterior commissure, optic nerve, cervical spinal cord and sciatic nerve. Samples were examined by immunohistochemistry, in situ hybridization for myelin proteins and myelin protein mRNA-s, respectively. Conventional neuropathological stainings and electron microscopy was also performed.
Results: Oligodendrocyte degeneration and demyelination followed a particular standard pattern in the central nervous system. Profound myelin loss developed in the superior cerebellar peduncle, anterior commissure and corpus callosum, whereas the optic nerves, velum medullare anterior and spinal cord showed little or no demyelination. Sciatic nerves were unaffected. No infiltration by lymphocytes or blood-brain barrier damage was observed during cuprizone treatment.
Conclusion: Cuprizone induced oligodendrocyte damage and demyelination follows a particular standard pattern in the central nervous system of mice. Cuprizone induced demyelination might be considered as a model for human demyelinating disorders with primary oligodendrocyte dystrophy and apoptosis.