title: Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond.
abstract: Although the primary cause of multiple sclerosis (MS) is unknown, the widely accepted view is that aberrant (auto)immune responses possibly arising following infection(s) are responsible for the destructive inflammatory demyelination and neurodegeneration in the central nervous system (CNS). This notion, and the limited access of human brain tissue early in the course of MS, has led to the development of autoimmune, viral and toxin-induced demyelination animal models as well as the development of human CNS cell and organotypic brain slice cultures in an attempt to understand events in MS. The autoimmune models, collectively known as experimental autoimmune encephalomyelitis (EAE), and viral models have shaped ideas of how environmental factors may trigger inflammation, demyelination and neurodegeneration in the CNS. Understandably, these models have also heavily influenced the development of therapies targeting the inflammatory aspect of MS. Demyelination and remyelination in the absence of overt inflammation are better studied in toxin-induced demyelination models using cuprizone and lysolecithin. The paradigm shift of MS as an autoimmune disease of myelin to a neurodegenerative disease has required more appropriate models reflecting the axonal and neuronal damage. Thus, secondary progressive EAE and spastic models have been crucial to develop neuroprotective approaches. In this review the current in vivo and in vitro experimental models to examine pathological mechanisms involved in inflammation, demyelination and neuronal degeneration, as well as remyelination and repair in MS are discussed. Since this knowledge is the basis for the development of new therapeutic approaches for MS, we particularly address whether the currently available models truly reflect the human disease, and discuss perspectives to further optimise and develop more suitable experimental models to study MS.
authors: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands; Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors: Markus
authors: M
authors: Kipp
authors: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors: Baukje
authors: B
authors: van der Star
authors: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands; Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Daphne Y S
authors: DY
authors: Vogel
authors: Neuroimmunology Unit, Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
authors: Fabìola
authors: F
authors: Puentes
authors: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors: Paul
authors: P
authors: van der Valk
authors: Neuroimmunology Unit, Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
authors: David
authors: D
authors: Baker
authors: Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands; Neuroimmunology Unit, Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK. Electronic address: s.amor@vumc.nl.
authors: Sandra
authors: S
authors: Amor
keywords: Blood–brain barrier; Cuprizone; EAE; In vitro; Neurodegeneration; Virus models