Table 1.

Animal Models of Experimental Demyelination

Model	Mechanism	Aspect(s) of MS Modeled	Pros	Cons
Autoimmune experimental autoimmune/ allergic encephalomy- elitis (EAE)	Co-injection of pertussis toxin and a specific myelin protein (MOG,MBP, or PLP) causes myelin destruction mediated primarily by invasion of peripheral antigen-specific T cells.	myelin destruction systemic inflammation immune surveillance Immune-mediated tissue destruction	Led to the development of 3 FDA-approved therapies1 Closely models post-vaccinal encephalitis2	Poor model for remyelination due to stochastic lesion location and occurrence3 Many approaches developed in EAE fail in human trials4 Lacks classic features of auto-immunity1 EAE lesions are dominated by CD4+ T-cells, compared to CD8+ T-cells in human lesions1
Theiler’s murine encephalomy elitis virus (TMEV)	Intracerebral infection with TMEV in susceptible mouse strains leads to chronic demyelination primarily in the spinal cord.	chronic progressive demyelination autoimmune response triggered by viral infection	demyelination is immunemediated1 chronic demyelination persists throughout lifespan1 recapitulates several MS features by small animal MRI and MRS1	Mechanism of demyelination is unknown Primarily models the contribution of viruses
Toxin Induced Models:
Lysolecithin	Focal injection of 1% lysolecithin, an activator of phospholipase A2, into the spinal cord produces local demyelination.	myelin destruction remyelination	Useful for identifying proremyelination therapies3 spatiotemporal predictability fosters the study of discrete mechanisms mediating the demyelination and remyelination processes3	Demyelination is not immune-mediated1 Absence of ongoing immune activity3 mechanism of lysolecithin toxicity is unknown
Cuprizone	Administration of 0.2% cuprizone, a copper chelator, in the chow leads to mitochondrial complex IV dysfunction and oligodendrocyte toxicity, leading to demyelination in the corpus callosum and hippocampus.	oligodendrocyte death myelin destruction remyelination	Can be used to model chronic demyelination with continued feeding Useful for identifying pro-remyelination therapies3 Lesions resemble pattern III human MS lesions3 Lesion development closely mimics that of human MS lesions, with demyelination and remyelination coinciding3	Overlap of demyelination and remyelination can confound interpretation3

¹(Denic et al., 2011),

²(Baxter, 2007),

³(Ransohoff, 2012),

⁴(Sriram and Steiner, 2005)