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Experimental In Vivo Models for Drug Discovery in Multiple Sclerosis

Leyre Mestre, Carmen Guaza

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Abstract

Multiple sclerosis (MS) is the most common chronic demyelinating inflammatory disease of the central nervous system (CNS). Although it is a pathology only described in humans, there are several well-established animal models that are postulated as fundamental tools not only for elucidating the origin of the pathology (unknown to date), but also to develop new therapeutic drugs to slow down the disease progression. The main models of MS are classified according to the hypothetical origin of the pathology in “immune-mediated”, “virus-induced” and “toxin-induced” models. The experimental autoimmune encephalomyelitis (EAE) is the best characterized immune-mediated model to explore different aspects of autoimmunity in MS pathology. Regarding the virus-induced model, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) allows not only the study of a large part of the histopathological and clinical signs, but also takes into account the hypothesis that viral infections would trigger an autoimmune disease. Toxin-induced models such as ethidium bromide, lysolecithin or cuprizone are useful for the evaluation of demyelination/remyelination processes. Throughout this chapter we will address the above experimental models from the perspective of the etiopathogenesis of MS and for the development of new potential therapeutic drugs.

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What this paper is about

Multiple sclerosis (MS) is the most common chronic demyelinating inflammatory disease of the central nervous system (CNS). Although it is a pathology only described in humans, there are several well-established animal models that are postulated as fundamental tools not only for elucidating the origin of the pathology (unknown to date), but also to develop new therapeutic drugs to slow down the disease progression. The main models of MS are classified according to the hypothetical origin of the pathology in “immune-mediated”, “virus-induced” and “toxin-induced” models. The experimental autoimmune encephalomyelitis (EAE) is the best characterized immune-mediated model to explore different aspects of autoimmunity in MS pathology. Regarding the virus-induced model, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) allows not only the study of a large part of the histopathological and clinical signs, but also takes into account the hypothesis that viral infections would trigger an autoimmune disease. Toxin-induced models such as ethidium bromide, lysolecithin or cuprizone are useful for the evaluation of demyelination/remyelination processes. Throughout this chapter we will address the above experimental models from the perspective of the etiopathogenesis of MS and for the development of new potential therapeutic drugs.

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Available abstract

Multiple sclerosis (MS) is the most common chronic demyelinating inflammatory disease of the central nervous system (CNS). Although it is a pathology only described in humans, there are several well-established animal models that are postulated as fundamental tools not only for elucidating the origin of the pathology (unknown to date), but also to develop new therapeutic drugs to slow down the disease progression. The main models of MS are classified according to the hypothetical origin of the pathology in “immune-mediated”, “virus-induced” and “toxin-induced” models. The experimental autoimmune encephalomyelitis (EAE) is the best characterized immune-mediated model to explore different aspects of autoimmunity in MS pathology. Regarding the virus-induced model, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) allows not only the study of a large part of the histopathological and clinical signs, but also takes into account the hypothesis that viral infections would trigger an autoimmune disease. Toxin-induced models such as ethidium bromide, lysolecithin or cuprizone are useful for the evaluation of demyelination/remyelination processes. Throughout this chapter we will address the above experimental models from the perspective of the etiopathogenesis of MS and for the development of new potential therapeutic drugs.

Key concepts: Remyelination, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Demyelinating disease, Encephalomyelitis, Immune system, Disease, Medicine

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