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:	Katie Lidster, Samuel J Jackson, Zubair Ahmed, Peter Munro, Pete Coffey, Gavin Giovannoni, Mark D Baker, David Baker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25c87925b0f24c17a681f38b45d83852
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spelling	oai:doaj.org-article:25c87925b0f24c17a681f38b45d838522021-11-18T08:48:29ZNeuroprotection in a novel mouse model of multiple sclerosis.1932-620310.1371/journal.pone.0079188https://doaj.org/article/25c87925b0f24c17a681f38b45d838522013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223903/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple 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.Katie LidsterSamuel J JacksonZubair AhmedPeter MunroPete CoffeyGavin GiovannoniMark D BakerDavid BakerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79188 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katie Lidster Samuel J Jackson Zubair Ahmed Peter Munro Pete Coffey Gavin Giovannoni Mark D Baker David Baker Neuroprotection in a novel mouse model of multiple sclerosis.
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.
format	article
author	Katie Lidster Samuel J Jackson Zubair Ahmed Peter Munro Pete Coffey Gavin Giovannoni Mark D Baker David Baker
author_facet	Katie Lidster Samuel J Jackson Zubair Ahmed Peter Munro Pete Coffey Gavin Giovannoni Mark D Baker David Baker
author_sort	Katie Lidster
title	Neuroprotection in a novel mouse model of multiple sclerosis.
title_short	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_sort	neuroprotection in a novel mouse model of multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/25c87925b0f24c17a681f38b45d83852
work_keys_str_mv	AT katielidster neuroprotectioninanovelmousemodelofmultiplesclerosis AT samueljjackson neuroprotectioninanovelmousemodelofmultiplesclerosis AT zubairahmed neuroprotectioninanovelmousemodelofmultiplesclerosis AT petermunro neuroprotectioninanovelmousemodelofmultiplesclerosis AT petecoffey neuroprotectioninanovelmousemodelofmultiplesclerosis AT gavingiovannoni neuroprotectioninanovelmousemodelofmultiplesclerosis AT markdbaker neuroprotectioninanovelmousemodelofmultiplesclerosis AT davidbaker neuroprotectioninanovelmousemodelofmultiplesclerosis
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Neuroprotection in a novel mouse model of multiple sclerosis.

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