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Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures

Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high do...

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Autores principales: Pingel, Jessica, Nielsen, Mikkel Schou, Lauridsen, Torsten, Rix, Kristian, Bech, Martin, Alkjaer, Tine, Andersen, Ida Torp, Nielsen, Jens Bo, Feidenhansl, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677119/
https://www.ncbi.nlm.nih.gov/pubmed/29116170
http://dx.doi.org/10.1038/s41598-017-14997-3
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author Pingel, Jessica
Nielsen, Mikkel Schou
Lauridsen, Torsten
Rix, Kristian
Bech, Martin
Alkjaer, Tine
Andersen, Ida Torp
Nielsen, Jens Bo
Feidenhansl, R.
author_facet Pingel, Jessica
Nielsen, Mikkel Schou
Lauridsen, Torsten
Rix, Kristian
Bech, Martin
Alkjaer, Tine
Andersen, Ida Torp
Nielsen, Jens Bo
Feidenhansl, R.
author_sort Pingel, Jessica
collection PubMed
description Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
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spelling pubmed-56771192017-11-15 Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures Pingel, Jessica Nielsen, Mikkel Schou Lauridsen, Torsten Rix, Kristian Bech, Martin Alkjaer, Tine Andersen, Ida Torp Nielsen, Jens Bo Feidenhansl, R. Sci Rep Article Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait. Nature Publishing Group UK 2017-11-07 /pmc/articles/PMC5677119/ /pubmed/29116170 http://dx.doi.org/10.1038/s41598-017-14997-3 Text en © The Author(s) 2017 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
Pingel, Jessica
Nielsen, Mikkel Schou
Lauridsen, Torsten
Rix, Kristian
Bech, Martin
Alkjaer, Tine
Andersen, Ida Torp
Nielsen, Jens Bo
Feidenhansl, R.
Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title_full Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title_fullStr Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title_full_unstemmed Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title_short Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
title_sort injection of high dose botulinum-toxin a leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677119/
https://www.ncbi.nlm.nih.gov/pubmed/29116170
http://dx.doi.org/10.1038/s41598-017-14997-3
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