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4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury
Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4‐aminopyridine (4‐AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167128/ https://www.ncbi.nlm.nih.gov/pubmed/27861125 http://dx.doi.org/10.15252/emmm.201506035 |
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author | Tseng, Kuang‐Ching Li, Haiyan Clark, Andrew Sundem, Leigh Zuscik, Michael Noble, Mark Elfar, John |
author_facet | Tseng, Kuang‐Ching Li, Haiyan Clark, Andrew Sundem, Leigh Zuscik, Michael Noble, Mark Elfar, John |
author_sort | Tseng, Kuang‐Ching |
collection | PubMed |
description | Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4‐aminopyridine (4‐AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promise as a small molecule regenerative agent for acute traumatic nerve injury. We found, in a mouse model of sciatic crush injury, that sustained early 4‐AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration. Further studies demonstrated that 4‐AP also enhanced recovery of nerve conduction velocity, promoted remyelination, and increased axonal area post‐injury. We additionally found that 4‐AP treatment enables distinction between incomplete and complete lesions more rapidly than existing approaches, thereby potentially addressing the critical challenge of more effectively distinguishing injured individuals who may require mutually exclusive treatment approaches. Thus, 4‐AP singularly provides both a new potential therapy to promote durable recovery and remyelination in acute peripheral nerve injury and a means of identifying lesions in which this therapy would be most likely to be of value. |
format | Online Article Text |
id | pubmed-5167128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51671282016-12-28 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury Tseng, Kuang‐Ching Li, Haiyan Clark, Andrew Sundem, Leigh Zuscik, Michael Noble, Mark Elfar, John EMBO Mol Med Research Articles Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4‐aminopyridine (4‐AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promise as a small molecule regenerative agent for acute traumatic nerve injury. We found, in a mouse model of sciatic crush injury, that sustained early 4‐AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration. Further studies demonstrated that 4‐AP also enhanced recovery of nerve conduction velocity, promoted remyelination, and increased axonal area post‐injury. We additionally found that 4‐AP treatment enables distinction between incomplete and complete lesions more rapidly than existing approaches, thereby potentially addressing the critical challenge of more effectively distinguishing injured individuals who may require mutually exclusive treatment approaches. Thus, 4‐AP singularly provides both a new potential therapy to promote durable recovery and remyelination in acute peripheral nerve injury and a means of identifying lesions in which this therapy would be most likely to be of value. John Wiley and Sons Inc. 2016-11-14 2016-12 /pmc/articles/PMC5167128/ /pubmed/27861125 http://dx.doi.org/10.15252/emmm.201506035 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Tseng, Kuang‐Ching Li, Haiyan Clark, Andrew Sundem, Leigh Zuscik, Michael Noble, Mark Elfar, John 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title | 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title_full | 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title_fullStr | 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title_full_unstemmed | 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title_short | 4‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
title_sort | 4‐aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167128/ https://www.ncbi.nlm.nih.gov/pubmed/27861125 http://dx.doi.org/10.15252/emmm.201506035 |
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