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Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy

Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal los...

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Autores principales: Dhillon, Rana S., Parker, John, Syed, Yasir A., Edgley, Steve, Young, Adam, Fawcett, James W., Jeffery, Nick D., Franklin, Robin J. M., Kotter, Mark R. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994254/
https://www.ncbi.nlm.nih.gov/pubmed/27552807
http://dx.doi.org/10.1186/s40478-016-0359-7
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author Dhillon, Rana S.
Parker, John
Syed, Yasir A.
Edgley, Steve
Young, Adam
Fawcett, James W.
Jeffery, Nick D.
Franklin, Robin J. M.
Kotter, Mark R. N.
author_facet Dhillon, Rana S.
Parker, John
Syed, Yasir A.
Edgley, Steve
Young, Adam
Fawcett, James W.
Jeffery, Nick D.
Franklin, Robin J. M.
Kotter, Mark R. N.
author_sort Dhillon, Rana S.
collection PubMed
description Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited. To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-016-0359-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-49942542016-08-24 Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy Dhillon, Rana S. Parker, John Syed, Yasir A. Edgley, Steve Young, Adam Fawcett, James W. Jeffery, Nick D. Franklin, Robin J. M. Kotter, Mark R. N. Acta Neuropathol Commun Research Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited. To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-016-0359-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-23 /pmc/articles/PMC4994254/ /pubmed/27552807 http://dx.doi.org/10.1186/s40478-016-0359-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Dhillon, Rana S.
Parker, John
Syed, Yasir A.
Edgley, Steve
Young, Adam
Fawcett, James W.
Jeffery, Nick D.
Franklin, Robin J. M.
Kotter, Mark R. N.
Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title_full Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title_fullStr Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title_full_unstemmed Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title_short Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
title_sort axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994254/
https://www.ncbi.nlm.nih.gov/pubmed/27552807
http://dx.doi.org/10.1186/s40478-016-0359-7
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