De- And Remyelination in the CNS White and Grey Matter Induced by Cuprizone: The Old, the New, and the Unexpected

Histol Histopathol. 2011 Dec;26(12):1585-97. doi: 10.14670/HH-26.1585.


The copper chelator cuprizone (bis-cyclohexanone oxaldihydrazone) was established as a neurotoxin in rodents in 1966 by Carlton. During the following years the usefulness of cuprizone feeding in mice to induce oligodendrocyte death with secondary demyelination of the superior cerebellar peduncles was described by Blakemore. In 1998 the cuprizone model experienced a renaissance as the group of Matsushima described the effects of cuprizone on the white matter of the cerebrum and focussed on demyelination in the corpus callosum, where the extent of demyelination could be scored more easily and consistently. Since then the toxic cuprizone model has been widely used to study experimental de- and remyelination in the corpus callosum. Recently, we and others have extended these studies and have shown several new aspects characteristic for this model. Many lessons can be learned from these recent findings that have implications for the basic understanding of remyelination and the design of remyelinating and neuroprotective strategies in demyelinating diseases of the CNS. Although the model is often mentioned in the context of multiple sclerosis, it must always be kept in mind that this model has a fundamentally different induction of demyelination. We highlight the important findings delineated from this model and critically discuss both the advantages and the shortcomings of cuprizone induced demyelination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / pathology
  • Chelating Agents / toxicity*
  • Cuprizone / toxicity*
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath / drug effects*
  • Myelin Sheath / pathology
  • Neuroprotective Agents / pharmacology
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Species Specificity


  • Chelating Agents
  • Neuroprotective Agents
  • Cuprizone