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Rapid and robust restoration of breathing long after spinal cord injury

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of ch...

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Autores principales: Warren, Philippa M., Steiger, Stephanie C., Dick, Thomas E., MacFarlane, Peter M., Alilain, Warren J., Silver, Jerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258702/
https://www.ncbi.nlm.nih.gov/pubmed/30482901
http://dx.doi.org/10.1038/s41467-018-06937-0
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author Warren, Philippa M.
Steiger, Stephanie C.
Dick, Thomas E.
MacFarlane, Peter M.
Alilain, Warren J.
Silver, Jerry
author_facet Warren, Philippa M.
Steiger, Stephanie C.
Dick, Thomas E.
MacFarlane, Peter M.
Alilain, Warren J.
Silver, Jerry
author_sort Warren, Philippa M.
collection PubMed
description There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess serotonergic (5HT) axon sprouting leading to aberrant tonic activity in the diaphragm that could be mitigated via 5HT2 receptor blockade. Through unmasking of the continuing neuroplasticity that develops after injury, our treatment strategy ensured rapid and robust patterned respiratory recovery after a near lifetime of paralysis.
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spelling pubmed-62587022018-11-29 Rapid and robust restoration of breathing long after spinal cord injury Warren, Philippa M. Steiger, Stephanie C. Dick, Thomas E. MacFarlane, Peter M. Alilain, Warren J. Silver, Jerry Nat Commun Article There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess serotonergic (5HT) axon sprouting leading to aberrant tonic activity in the diaphragm that could be mitigated via 5HT2 receptor blockade. Through unmasking of the continuing neuroplasticity that develops after injury, our treatment strategy ensured rapid and robust patterned respiratory recovery after a near lifetime of paralysis. Nature Publishing Group UK 2018-11-27 /pmc/articles/PMC6258702/ /pubmed/30482901 http://dx.doi.org/10.1038/s41467-018-06937-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Warren, Philippa M.
Steiger, Stephanie C.
Dick, Thomas E.
MacFarlane, Peter M.
Alilain, Warren J.
Silver, Jerry
Rapid and robust restoration of breathing long after spinal cord injury
title Rapid and robust restoration of breathing long after spinal cord injury
title_full Rapid and robust restoration of breathing long after spinal cord injury
title_fullStr Rapid and robust restoration of breathing long after spinal cord injury
title_full_unstemmed Rapid and robust restoration of breathing long after spinal cord injury
title_short Rapid and robust restoration of breathing long after spinal cord injury
title_sort rapid and robust restoration of breathing long after spinal cord injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258702/
https://www.ncbi.nlm.nih.gov/pubmed/30482901
http://dx.doi.org/10.1038/s41467-018-06937-0
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