The cuprizone model for demyelination

Abstract

The cuprizone model correlates with newer histopathological data in MS and is a valuable tool for studies on de- and remyelination. The use of the C57BL/6 strain offers the potential for future studies on transgene and knockout mice.

A cord blood monocyte–derived cell therapy product accelerates brain remyelination

“…To accomplish this, we assessed the ability of DUOC-01 to promote remyelination of mouse brain after cuprizone-induced (CPZ-induced) demyelination, a model that has been widely used to study the mechanisms and cellular dynamics of remyelination in the corpus callosum (CC) region (21)(22)(23)(24)(25)(26), and also to test the effects of various interventions, including cell therapy agents (27)(28)(29)(30). CPZ is a Cu ++ -chelating agent that is highly toxic to oligodendrocytes (26,(31)(32)(33)(34), and CPZ feeding results in demyelination that can be assessed in the CC where abundant neural fiber bundles become disorganized as myelin degrades.…”

Superantigen-Mediated Encephalitis

“…There are, however, different states of aseptic encephalitis, which may be induced e.g. by way of (i) self-directed immune attacks as in experimental autoimmune encephalomyelitis or (ii) by certain substances like the copper chelating agent cuprizone (Torkildsen et al, 2008). In fact, in encephalitis, infectious and non-infectious processes do not mutually exclude each other.…”

Functional implications of demyelination and the molecular control of remyelination in the adult mouse.

“…However, it is unclear whether miRNAs involved in remyelination are distinct from those observed during normal myelination / development. Treatment of adult mice with the viii copper chelator cuprizone demyelinates specific brain regions which remyelinate following cuprizone cessation (Torkildsen et al, 2008). Therefore, Chapter 4…”

“…In rats, toxic demyelination models using ethidium bromide (EB; Blakemore and Franklin; and lysolecithin (Gregson and Hall, 1973) as well as trauma-induced demyelination (SCI; Totoiu and Keirstead, 2005) have provided a platform to assess remyelination which takes advantage of the advanced behavioral assessment methods available for rat studies (Onifer et al, 2007). In mice, cuprizone ingestion (Torkildsen et al, 2008), experimental autoimmune encephalopathy (EAE; Constantinescu et al, 2011) and mutant strains of mice lacking in genes necessary for myelin formation (Windrem et al, 2008;Wang et al, 2013) have all been used as a platform to assess remyelination. Of all rodent demyelination models, low concentration EB (Franklin and ffrench-Constant, 2008) and lysolecithin (Jeffery and Blakemore, 1995) injection as well as the cessation of cuprizone demyelination ) each exhibit a spontaneous remyelination response which is driven by OPs.…”

“…Oxalic bis-cyclohexylidenehydrazide (cuprizone) is a copper chelator which can be administered to mice in chow to induce CNS demyelination, most notably in the corpus callosum (Steelman et al, 2008). The cuprizone model has been well described and is commonly employed as a 6 week on cuprizone ingestion period (demyelination) followed by a 6 week recovery period (remyelination) where mice are returned to normal chow (Torkildsen et al, 2008). This remyelination response is driven by OPs and is observed during both the later part of the ingestion phase and throughout the recovery (Mason et al, 2001;Matsushima and Morell, 2001).…”