title: In vitro and in vivo models of multiple sclerosis.
abstract: Multiple sclerosis (MS) is widely considered to be the result of an aggressive autoreactive T cell attack on myelin. How these autoimmune responses arise in MS is unclear, but they could result from virus infections. Thus, viral and autoimmune diseases in animals have been used to investigate the possible pathogenic mechanisms operating in MS. The autoimmune model, experimental autoimmune encephalomyelitis, is the most widely-used animal model and has greatly influenced therapeutic approaches targeting autoimmune responses. To investigate demyelination and remyelination in the absence of the adaptive immune response, toxin-induced demyelination models are used. These include using cuprizone, ethidium bromide and lysolecithin to induce myelin damage, which rapidly lead to remyelination when the toxins are withdrawn. The virus models include natural and experimental infections such as canine distemper, visna infection of sheep, and infection of non-human primates. The most commonly used viral models in rodents are Semliki Forest virus and Theiler's murine encephalomyelitis virus. The viral and experimental autoimmune encephalomyelitis models have been instrumental in the understanding of how viruses trigger inflammation, demyelination and neurodegeneration in the central nervous system. However, due to complexity of the animal models, pathological mechanisms are also examined in central nervous system cell culture systems including co-cultures, aggregate cultures and brain slice cultures. Here we critically review in vitro and in vivo models used to investigate MS. Since knowledge gained from these models forms the basis for the development of new therapeutic approaches for MS, we address the applicability of the models. Finally, we provide guidance for using and reporting animal studies with the aim of improving translational studies to the clinic.
authors.affiliation: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Baukje J
authors.initials: BJ
authors.lastname: van der Star
authors.forename: Daphne Y S
authors.initials: DY
authors.lastname: Vogel
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Fabiola
authors.initials: F
authors.lastname: Puentes
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001369:Axons / Q000276:immunology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology*