Mechanism of Cuprizone Demyelination

[NHE]

Many research papers now use cuprizone induced demyelination as a model for studying MS.

Here's a few things we know about cuprizone.

Cuprizone is a copper chelator.
Cuprizone causes widespread demyelination which differs from the more punctate lesions seen in MS.
The blood brain barrier remains intact.
There is no recruitment of T-cells.
Cuprizone is thought to induce iron related toxicity in oligodendrocytes.
Withdrawal of cuprizone allows for spontaneous remyelination.
Cuprizone does not produce an inflammatory phase as seen in RRMS, but does cause macrophage activation.
Cuprizone may act through mitochondrial toxicity due to disruption of copper cofactor based enzymatic activity, e.g., cytochrome c oxidase.

https://www.sciencedirect.com/topics/me ... /cuprizone
https://pubmed.ncbi.nlm.nih.gov/33106352/
https://www.researchgate.net/publicatio ... yelination

Is cuprizone induced demyelination a valid model for studying MS or just a convenient model? That's a difficult question to answer.