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Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair

BACKGROUND: Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. A...

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Autores principales: Vest, Maxwell, Guida, Addison, Colombini, Cory, Cordes, Kristina, Pena, Diana, Maki, Marwa, Briones, Michael, Antonio, Sabrina, Hollifield, Carmen, Tian, Elli, James, Lucas, Borashan, Christian, Woodson, Johnnie, Rovig, John, Shihadeh, Hanaa, Karabachev, Alexander, Brosious, John, Pistorio, Ashley
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JMIR Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484768/
https://www.ncbi.nlm.nih.gov/pubmed/32851981
http://dx.doi.org/10.2196/18706
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author Vest, Maxwell
Guida, Addison
Colombini, Cory
Cordes, Kristina
Pena, Diana
Maki, Marwa
Briones, Michael
Antonio, Sabrina
Hollifield, Carmen
Tian, Elli
James, Lucas
Borashan, Christian
Woodson, Johnnie
Rovig, John
Shihadeh, Hanaa
Karabachev, Alexander
Brosious, John
Pistorio, Ashley
author_facet Vest, Maxwell
Guida, Addison
Colombini, Cory
Cordes, Kristina
Pena, Diana
Maki, Marwa
Briones, Michael
Antonio, Sabrina
Hollifield, Carmen
Tian, Elli
James, Lucas
Borashan, Christian
Woodson, Johnnie
Rovig, John
Shihadeh, Hanaa
Karabachev, Alexander
Brosious, John
Pistorio, Ashley
author_sort Vest, Maxwell
collection PubMed
description BACKGROUND: Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection. OBJECTIVE: This study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction. METHODS: This study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons. RESULTS: The author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021. CONCLUSIONS: In this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18706
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spelling pubmed-74847682020-09-21 Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair Vest, Maxwell Guida, Addison Colombini, Cory Cordes, Kristina Pena, Diana Maki, Marwa Briones, Michael Antonio, Sabrina Hollifield, Carmen Tian, Elli James, Lucas Borashan, Christian Woodson, Johnnie Rovig, John Shihadeh, Hanaa Karabachev, Alexander Brosious, John Pistorio, Ashley JMIR Res Protoc Protocol BACKGROUND: Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection. OBJECTIVE: This study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction. METHODS: This study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons. RESULTS: The author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021. CONCLUSIONS: In this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18706 JMIR Publications 2020-08-27 /pmc/articles/PMC7484768/ /pubmed/32851981 http://dx.doi.org/10.2196/18706 Text en ©Maxwell Vest, Addison Guida, Cory Colombini, Kristina Cordes, Diana Pena, Marwa Maki, Michael Briones, Sabrina Antonio, Carmen Hollifield, Elli Tian, Lucas James, Christian Borashan, Johnnie Woodson, John Rovig, Hanaa Shihadeh, Alexander Karabachev, John Brosious, Ashley Pistorio. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 27.08.2020. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.
spellingShingle Protocol
Vest, Maxwell
Guida, Addison
Colombini, Cory
Cordes, Kristina
Pena, Diana
Maki, Marwa
Briones, Michael
Antonio, Sabrina
Hollifield, Carmen
Tian, Elli
James, Lucas
Borashan, Christian
Woodson, Johnnie
Rovig, John
Shihadeh, Hanaa
Karabachev, Alexander
Brosious, John
Pistorio, Ashley
Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title_full Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title_fullStr Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title_full_unstemmed Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title_short Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair
title_sort closing the gap between mammalian and invertebrate peripheral nerve injury: protocol for a novel nerve repair
topic Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484768/
https://www.ncbi.nlm.nih.gov/pubmed/32851981
http://dx.doi.org/10.2196/18706
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