The ultrastructural features of the encephalopathy induced by chronic feeding of cuprizone in the white matter of the cerebellar medulla of mice were characterized. Mice were fed a diet of 0.5% cuprizone for 8 wk and, under anesthesia, were perfused with 6% buffered glutaraldehyde. Small pieces of the cerebellar peduncles were post-fixed in 1% phosphate-buffered osmium tetroxide and embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate and examined with the RCA-EMU-3f electron microscope. Ultrastructural alterations were observed in the astrocytes, oligodendrocytes, axoplasm, myelin, and extracellular space. Some astrocytes had a pale electron lucent cytoplasm, while in other astrocytes, vacuoles, foci of proliferated fibrils, and focal cytoplasmic clearings were found. Myelin figures, vacuoles, structured dense bodies, and proliferated profiles of rough-surfaced endoplasmic reticulum occurred in the cytoplasm of oligodendrocytes. The histologic vacuolation was apparently the result of intramyelinic and glial vacuolation observed in the electron micrographs. Edemia fluid occurred infrequently in the extracellular space. Dystrophic changes were observed in the axoplasm of some axons and consisted of the accumulation of dense bodies and vesicles. Occasionally, proliferation of the mesaxon was found, and when present, it displaced the axoplasm. © 1971.
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