Experimental In Vivo Models of Multiple Sclerosis: State of the Art

Abstract

Abstract: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), cuprizone 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 flexible 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 mechanisms of acute and primary progressive multiple sclerosis. In Vivo Models of Multiple Sclerosis 174

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

“…Box 2. Virus-Induced Animal Models of Inflammation, Demyelination, and DegenerationAnimal models can be used to explore virus-specific mechanisms contributing to autoimmune and demyelinating diseases including MS[95][96][97]. EBV itself does not infect mice, which has contributed to the challenge of studying the role of EBV in models of CNS inflammation including experimental autoimmune encephalomyelitis (EAE).…”

The role of chemokines and chemokine receptors in multiple sclerosis

“…The EAE model is relevant for RRMS mostly. MOG induces chronic progressive disease which is closer to SPMS in C57BL/6 mice whereas chronic relapsing-remitting disease in NOD/Lt and SJL mice and Lewis rats [87], non-classical chronic relapsing EAE in PL/J mice. MOG -immunized NOD mice will first develop an acute episode of EAE and then undergo a secondary progressive EAE course.…”

“…Current MS phenotypic classifications contain RRMS, CIS, PPMS and SPMS, which means relapsing-remitting multiple sclerosis, clinically isolated syndrome, primary-progressive multiple sclerosis, and secondary-progressive multiple sclerosis respectively [71]. Among them, RRMS accounts for the majority of patients (about 80%) [87]. The hallmark of MS is leukocyte infiltration of brain tissue and subsequent axonal injury, demyelination inflammation and the formation of sclerosing plaques [54].…”

“…Classically studied animal models of MS are (1) allergic encephalomyelitis/experimental autoimmune (EAE); (2) virus-induced models and (3) toxin-induced demyelination models [90].Experimental autoimmune encephalomyelitis (abbreviated as EAE), an experimental animal model of human MS, is obtained by using myelin oligodendrocyte protein(MOG), proteolipid protein(PLP) or myelin basic protein (MBP) immuning and inducing in certain susceptible experimental animals such as mice and other rodents [44]. Besides, EAE can be triggered by the adoptive transfer of myelin antigen-specific T cells, CD8 + T lymphocytes and Th1 and Th17 type CD4 + cells [66,87]. The pathogenesis of EAE consists of two phases.…”

“…Among them, the CPZ model simulates the acute and chronic courses of MS and may be a useful tool for the development of new therapies that protect oligodendrocytes and stimulate myelin regeneration. The TMEV infection model is an animal model that specializes in studying the mechanisms of virus-mediated acute and primary progressive MS [87].Chemokines regulate lymphoid tissue development, lymphocyte transport, and homing, and leukocyte maturation as we all know [10]. In autoimmune diseases such as MS, characterized by uncontrolled inflammatory states and increased immune cell infiltration into tissue parenchyma, upregulated expression of chemokines is associated with elevated infiltration of macrophages, monocytes, and lymphocytes in lesions and plaques [62].…”