Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Alilain, Warren J., Horn, Kevin P., Hu, Hongmei, Dick, Thomas E., Silver, Jerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
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
_version_ 1782210946359361536
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
work_keys_str_mv AT alilainwarrenj functionalregenerationofrespiratorypathwaysafterspinalcordinjury
AT hornkevinp functionalregenerationofrespiratorypathwaysafterspinalcordinjury
AT huhongmei functionalregenerationofrespiratorypathwaysafterspinalcordinjury
AT dickthomase functionalregenerationofrespiratorypathwaysafterspinalcordinjury
AT silverjerry functionalregenerationofrespiratorypathwaysafterspinalcordinjury