The cuprizone model of demyelination/remyelination is induced by feeding mice the copper-chelating cuprizone toxin. Cuprizone administration models several aspects of human multiple sclerosis (MS), including demyelination, spontaneous remyelination, oligodendrocyte precursor cell (OPC) proliferation & maturation, astrogliosis, and microgliosis. The pathology in the cuprizone model is primarily limited to the corpus callosum with highly predictable pathology.
Unlike EAE, cuprizone is not autoimmune mediated and the demyelination/remyelination is not confounded by a peripheral immune response. EAE and cuprizone model different aspects of MS pathology, and therapeutic studies are often performed in parallel.
- C57BL/6 mice are fed 0.2-0.3% cuprizone via powdered chow, food pellets, or oral gavage
- A more severe, chronic model can be generated by injecting rapamycin (i.p. 5 days per week)
- In our experience, the powdered chow route of administration provides the most reproducible results
Our Validated Measures
- Body weight
- Myelin-sensitive in vivo MRI
- Immunohistochemistry & multiplex immunofluorescence of the corpus callosum
Learn more about our characterization of this model and our validated measures.
Discover more of our Multiple Sclerosis Models
What are the advantages of in vivo MRI for the cuprizone model?
We use the Magnetization Transfer Ratio (MTR) to assess demyelination and remyelination this model.
Key advantages include:
- Clinically translational measure that is widely used in MS clinical trials
- Longitudinal assessment in the same animal
- In-life readout for faster go/no-go decision-making
What is the typical time course of demyelination and remyelination in the cuprizone model?
Here is an illustration of a typical time course:
Is inflammation observed in the cuprizone model?
Cuprizone is an excellent model of neuroinflammation (microgliosis and astrogliosis). Here is a typical time course:
Unlike EAE, it does not show significant peripheral inflammatory infiltrates, such as T cells.
Can cuprizone and EAE studies be performed in parallel?
Yes. Since cuprizone and EAE model different aspects of human MS, they can be run as parallel studies for a comprehensive assessment of therapeutic agents on demyelination, remyelination, neuroinflammation, peripheral inflammation, axonal damage, etc.
What is the cuprizone-rapamycin model?
By adding rapamycin (typically i.p. administration 5 days per week) to the cuprizone model, a more severe model can be generated. The option to include rapamycin in the model generation depends on your therapeutic agent and the questions that you are trying to answer. Our MS model scientists would be happy to discuss the pros and cons of this model with you.