Experimental in vivo models of multiple sclerosis: state of the art

Multiple sclerosis is a multifactorial and heterogeneous neurological disease; hence, several experimental animal models had to be developed to mimic the different features of human pathology. Three main classes of animal models have been developed:experimental autoimmune encephalomyelitis (EAE), cupri- zone intoxication, and Theiler’s murine encephalomyelitis virus (TMEV) infection. The EAE model is the most versatile as it allows the reproduction of different patterns of multiple sclerosis; it is mostly relevant for relapsing-remitting multiple sclerosis and has allowed the development of several first-line, disease-modifying drugs for the treatment of multiple sclerosis. The other two models are less flexi- ble than the EAE model and, to date, have not led to the discovery of any clinically relevant therapies. The cuprizone model mostly mimics the acute and chronic courses of multiple sclerosis, and it may represent a useful tool to develop novel therapies to protect oligodendrocytes and stimulate remyelination. Finally, the TMEV infection is the reference model to specifically study viral-mediated mecha- nisms of acute and primary progressive multiple sclerosis.