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Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strateg...

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Autores principales: Lidster, Katie, Jackson, Samuel J., Ahmed, Zubair, Munro, Peter, Coffey, Pete, Giovannoni, Gavin, Baker, Mark D., Baker, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817036/
https://www.ncbi.nlm.nih.gov/pubmed/24223903
http://dx.doi.org/10.1371/journal.pone.0079188
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author Lidster, Katie
Jackson, Samuel J.
Ahmed, Zubair
Munro, Peter
Coffey, Pete
Giovannoni, Gavin
Baker, Mark D.
Baker, David
author_facet Lidster, Katie
Jackson, Samuel J.
Ahmed, Zubair
Munro, Peter
Coffey, Pete
Giovannoni, Gavin
Baker, Mark D.
Baker, David
author_sort Lidster, Katie
collection PubMed
description Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment.
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spelling pubmed-38170362013-11-09 Neuroprotection in a Novel Mouse Model of Multiple Sclerosis Lidster, Katie Jackson, Samuel J. Ahmed, Zubair Munro, Peter Coffey, Pete Giovannoni, Gavin Baker, Mark D. Baker, David PLoS One Research Article Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment. Public Library of Science 2013-11-04 /pmc/articles/PMC3817036/ /pubmed/24223903 http://dx.doi.org/10.1371/journal.pone.0079188 Text en © 2013 Lidster et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lidster, Katie
Jackson, Samuel J.
Ahmed, Zubair
Munro, Peter
Coffey, Pete
Giovannoni, Gavin
Baker, Mark D.
Baker, David
Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title_full Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title_fullStr Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title_full_unstemmed Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title_short Neuroprotection in a Novel Mouse Model of Multiple Sclerosis
title_sort neuroprotection in a novel mouse model of multiple sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817036/
https://www.ncbi.nlm.nih.gov/pubmed/24223903
http://dx.doi.org/10.1371/journal.pone.0079188
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