Cuprizone neurotoxicity in the rat: morphologic observations.

Weanling male Wistar rats fed a diet containing 0.5-2% cuprizone developed intramyelinic edema of the cerebellar white matter, hilum of the dentate nucleus and superior cerebellar peduncle. Oligodendrocytes in these regions showed hyperchromatic nuclei and abnormally dense cytoplasm, with an increase in the number of free ribosomes and enlargement of mitochondria. Unlike the lesions produced by cuprizone in weanling mice, those in the rat did not lead to demyelination. Cuprizone caused a distal peripheral axonopathy, with degeneration of myelinated axons in the sciatic nerve but preservation of the spinal nerve roots, dorsal root ganglia, posterior spinal funiculi and anterior horn cells. Unmyelinated fibers were largely spared. Some axonal regeneration occurred despite the continued administration of cuprizone. The intramyelinic edema and the nuclear and cytoplasmic abnormalities of the oligodendrocytes disappeared after the resumption of a normal diet.