Modified Cuprizone Model of Remyelination
The cuprizone model captures several important attributes of MS and has been successfully used to test remyelination therapeutics. Cuprizone is a toxin that induces myelin damage by killing oligodendrocytes resulting in demyelination in both white and gray matter of the CNS. Although traditional cuprizone mouse model can mimic demyelination and remyelination processes, it has been difficult to test therapeutics because of significant variability in the level of demyelination. Renovo’s modified cuprizone model includes the co-administration rapamycin which inhibits spontaneous remyelination, providing a consistent demyelination. This results in a robust and reliable platform to evaluate remyelination as an independent process. Renovo offers both acute (6-week) and chronic (12-week) models of demyelination in both white and gray matter.
White Matter: The model captures the most important facet of white matter lesions by consistent and reliable demyelination and remyelination in the corpus callosum.
Gray Matter: Although MS is considered a white matter disease, increasing evidence shows that gray matter lesions are responsible for many aspects of MS. Renovo’s cuprizone model captures pathology of demyelination and remyelination in the cortex and hippocampus characteristic of MS.
Experimental End Points
- Grip strength – assess motor deficits
- Myelinated axons in corpus callosum
- Quantification of myelin in hippocampus
- Quantification of myelin in cortex
- Longitudinal in vivo MRI to evaluate myelin, functional MRI, structural MRI, etc.
- Electrophysiological assessment for compound action potential in the white matter region
- Additional histological quantification (OPCs, oligodendrocytes, microglia, astrocytes etc.)
- 3D-EM evaluation of myelin and axonal parameters