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Functional regeneration of respiratory pathways after spinal cord injury
Spinal cord injuries (SCI) often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. Unfortunately, the untoward effects of impaired breathing are a leading cause of SCI-related death, underscoring the importance of developing strategies to restore respiratory a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163458/ https://www.ncbi.nlm.nih.gov/pubmed/21753849 http://dx.doi.org/10.1038/nature10199 |
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author | Alilain, Warren J. Horn, Kevin P. Hu, Hongmei Dick, Thomas E. Silver, Jerry |
author_facet | Alilain, Warren J. Horn, Kevin P. Hu, Hongmei Dick, Thomas E. Silver, Jerry |
author_sort | Alilain, Warren J. |
collection | PubMed |
description | Spinal cord injuries (SCI) often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. Unfortunately, the untoward effects of impaired breathing are a leading cause of SCI-related death, underscoring the importance of developing strategies to restore respiratory activity. Here we show that after cervical SCI, there is upregulation of the perineuronal net (PNN) associated chondroitin sulfate proteoglycans (CSPGs) around phrenic motor neurons. Digestion of these potently inhibitory extracellular matrix molecules with Chondroitinase ABC (ChABC) can, by itself, promote plasticity of spared tracts and restore limited activity to the paralyzed diaphragm. However, when combined with application of a peripheral nerve autograft, ChABC treatment results in lengthy regeneration of serotonergic axons and other bulbospinal fibers with remarkable recovery of diaphragm function. Following recovery and initial transection of the bridge, there occurs an unusual, overall increased tonic diaphragmatic EMG activity, suggesting considerable remodeling of spinal cord circuitry after regeneration. This is followed by complete elimination of the restored activity proving that regeneration is critical for the return of function. Overall, these experiments present a way to profoundly restore function of a single muscle following debilitating CNS trauma, through both plasticity of spared tracts and regeneration of essential pathways. |
format | Online Article Text |
id | pubmed-3163458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-31634582012-01-14 Functional regeneration of respiratory pathways after spinal cord injury Alilain, Warren J. Horn, Kevin P. Hu, Hongmei Dick, Thomas E. Silver, Jerry Nature Article Spinal cord injuries (SCI) often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. Unfortunately, the untoward effects of impaired breathing are a leading cause of SCI-related death, underscoring the importance of developing strategies to restore respiratory activity. Here we show that after cervical SCI, there is upregulation of the perineuronal net (PNN) associated chondroitin sulfate proteoglycans (CSPGs) around phrenic motor neurons. Digestion of these potently inhibitory extracellular matrix molecules with Chondroitinase ABC (ChABC) can, by itself, promote plasticity of spared tracts and restore limited activity to the paralyzed diaphragm. However, when combined with application of a peripheral nerve autograft, ChABC treatment results in lengthy regeneration of serotonergic axons and other bulbospinal fibers with remarkable recovery of diaphragm function. Following recovery and initial transection of the bridge, there occurs an unusual, overall increased tonic diaphragmatic EMG activity, suggesting considerable remodeling of spinal cord circuitry after regeneration. This is followed by complete elimination of the restored activity proving that regeneration is critical for the return of function. Overall, these experiments present a way to profoundly restore function of a single muscle following debilitating CNS trauma, through both plasticity of spared tracts and regeneration of essential pathways. 2011-07-13 /pmc/articles/PMC3163458/ /pubmed/21753849 http://dx.doi.org/10.1038/nature10199 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Alilain, Warren J. Horn, Kevin P. Hu, Hongmei Dick, Thomas E. Silver, Jerry Functional regeneration of respiratory pathways after spinal cord injury |
title | Functional regeneration of respiratory pathways after spinal cord injury |
title_full | Functional regeneration of respiratory pathways after spinal cord injury |
title_fullStr | Functional regeneration of respiratory pathways after spinal cord injury |
title_full_unstemmed | Functional regeneration of respiratory pathways after spinal cord injury |
title_short | Functional regeneration of respiratory pathways after spinal cord injury |
title_sort | functional regeneration of respiratory pathways after spinal cord injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163458/ https://www.ncbi.nlm.nih.gov/pubmed/21753849 http://dx.doi.org/10.1038/nature10199 |
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