The Cuprizone Model – Diffuse Demyelinated Lesions
Oligodendrocyte cell death occurs as a result of the addition of the copper chelator, cuprizone to the diet of mice. The consequent demyelination is reversible as spontaneous remyelination can be observed as early as 4 days after removal of the neurotoxin. This makes the model a useful in-vivo tool for understanding the mechanics of remyelination without immune system interaction.
Cuprizone induced demyelination has a microglia and macrophage component and differs from MS and models of EAE as the blood brain barrier remains intact which may account for the lack of T cell involvement in the CNS.
We are currently developing our cuprizone model protocol:
C57BL/6 mice are fed 0.2% cuprizone supplemented animal chow for 6 weeks. Histology, MRI imaging and gene expression (mRNA) can provide data to quantify test compound effects.
Pharmaceutical intervention can be either prophylactic to reduce the level of demyelination or therapeutically to speed up the regeneration within lesions. Protocols would be adjusted in accordance with the therapeutic target and intended mechanism of action of the test compound.