Early regional cuprizone-induced demyelination in a rat model revealed with MRI

NMR Biomed. 2017 Sep;30(9). doi: 10.1002/nbm.3743. Epub 2017 May 22.

Abstract

The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum. In this study, we acquired high-resolution, three-dimensional images of the whole brain every 2 weeks, using a T1 -weighted magnetization-prepared rapid acquisition gradient echo imaging sequence, optimized for myelin contrast, in order to assess myelination across the entire rat brain over a period of 8 weeks on a 1% cuprizone diet. We observed a consistent pattern of demyelination, beginning in the cerebellum by 4 weeks and involving more rostral regions of the brain by 8 weeks on the cuprizone diet, with validation using Luxol fast blue histology. This imaging technique permits the effects of cuprizone-induced demyelination to be followed longitudinally in a single animal, over the entire brain. In turn, this may facilitate the establishment of the cuprizone model of demyelination in the rat.

Keywords: Animal model study; cuprizone; demyelination; myelin; neurological; post-acquisition processing; visualisation; white matter diseases.

MeSH terms

  • Animals
  • Contrast Media / chemistry
  • Cuprizone
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / diagnosis*
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Iron / metabolism
  • Liver / metabolism
  • Magnetic Resonance Imaging / methods*
  • Male
  • Myelin Sheath / pathology
  • Rats, Wistar
  • Signal Processing, Computer-Assisted

Substances

  • Contrast Media
  • Cuprizone
  • Iron