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Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury

Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrate...

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Autores principales: Zainul, Zarin, Ma, Bo, Koka, Mert, Wilkerson, Jenny L., Ortiz, Yuma T., Kerosuo, Laura, Chandran, Vijayendran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885794/
https://www.ncbi.nlm.nih.gov/pubmed/35228612
http://dx.doi.org/10.1038/s41598-022-07253-w
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author Zainul, Zarin
Ma, Bo
Koka, Mert
Wilkerson, Jenny L.
Ortiz, Yuma T.
Kerosuo, Laura
Chandran, Vijayendran
author_facet Zainul, Zarin
Ma, Bo
Koka, Mert
Wilkerson, Jenny L.
Ortiz, Yuma T.
Kerosuo, Laura
Chandran, Vijayendran
author_sort Zainul, Zarin
collection PubMed
description Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrates that phentolamine may hold a significant promise in treating nerve injuries and denervation induced muscle atrophy following PNI. In a sciatic nerve crush injury mouse model, we found that phentolamine treatment enhanced motor and functional recovery, protected axon myelination, and attenuated injury-induced muscle atrophy in mice at 14 days post-injury (dpi) compared to saline treatment. In the soleus of phentolamine treated animals, we observed the downregulation of phosphorylated signal transducer and activator of transcription factor 3 (p-STAT3) as well as muscle atrophy-related genes Myogenin, muscle ring finger 1 (MuRF-1), and Forkhead box O proteins (FoxO1, FoxO3). Our results show that both nerve and muscle recovery are integral components of phentolamine treatment-induced global functional recovery in mice at 14 dpi. Moreover, phentolamine treatment improved locomotor functional recovery in the mice after spinal cord crush (SCC) injury. The fact that phentolamine is an FDA approved non-selective alpha-adrenergic blocker, clinically prescribed for oral anesthesia reversal, hypertension, and erectile dysfunction makes this drug a promising candidate for repurposing in restoring behavioral recovery following PNI and SCC injuries, axonal neuropathy, and muscle wasting disorders.
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spelling pubmed-88857942022-03-01 Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury Zainul, Zarin Ma, Bo Koka, Mert Wilkerson, Jenny L. Ortiz, Yuma T. Kerosuo, Laura Chandran, Vijayendran Sci Rep Article Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrates that phentolamine may hold a significant promise in treating nerve injuries and denervation induced muscle atrophy following PNI. In a sciatic nerve crush injury mouse model, we found that phentolamine treatment enhanced motor and functional recovery, protected axon myelination, and attenuated injury-induced muscle atrophy in mice at 14 days post-injury (dpi) compared to saline treatment. In the soleus of phentolamine treated animals, we observed the downregulation of phosphorylated signal transducer and activator of transcription factor 3 (p-STAT3) as well as muscle atrophy-related genes Myogenin, muscle ring finger 1 (MuRF-1), and Forkhead box O proteins (FoxO1, FoxO3). Our results show that both nerve and muscle recovery are integral components of phentolamine treatment-induced global functional recovery in mice at 14 dpi. Moreover, phentolamine treatment improved locomotor functional recovery in the mice after spinal cord crush (SCC) injury. The fact that phentolamine is an FDA approved non-selective alpha-adrenergic blocker, clinically prescribed for oral anesthesia reversal, hypertension, and erectile dysfunction makes this drug a promising candidate for repurposing in restoring behavioral recovery following PNI and SCC injuries, axonal neuropathy, and muscle wasting disorders. Nature Publishing Group UK 2022-02-28 /pmc/articles/PMC8885794/ /pubmed/35228612 http://dx.doi.org/10.1038/s41598-022-07253-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zainul, Zarin
Ma, Bo
Koka, Mert
Wilkerson, Jenny L.
Ortiz, Yuma T.
Kerosuo, Laura
Chandran, Vijayendran
Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title_full Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title_fullStr Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title_full_unstemmed Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title_short Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
title_sort novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885794/
https://www.ncbi.nlm.nih.gov/pubmed/35228612
http://dx.doi.org/10.1038/s41598-022-07253-w
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