Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes

Introduction/Aims Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and re...

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Veröffentlicht in:Muscle & nerve 2023-01, Vol.67 (1), p.78-87
Hauptverfasser: Marsh, Evan B., Schellhardt, Lauren, Hunter, Daniel A., Mackinnon, Susan E., Snyder‐Warwick, Alison K., Wood, Matthew D.
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container_issue 1
container_start_page 78
container_title Muscle & nerve
container_volume 67
creator Marsh, Evan B.
Schellhardt, Lauren
Hunter, Daniel A.
Mackinnon, Susan E.
Snyder‐Warwick, Alison K.
Wood, Matthew D.
description Introduction/Aims Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and recovery more than either therapeutic alone. Methods Rats were randomized to four groups: E‐stim, FK506, FK506 + E‐stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21‐ and 42‐day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. Results Dual E‐stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P 
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Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and recovery more than either therapeutic alone. Methods Rats were randomized to four groups: E‐stim, FK506, FK506 + E‐stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21‐ and 42‐day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. Results Dual E‐stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E‐stim, P < .05; FK506 + E‐stim, P < .05). The E‐stim and FK506 + E‐stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E‐stim, P < .05; FK506 + E‐stim, P < .01). The FK506 group had improved recovery based on walking‐track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit. Discussion Dual administration of FK506 and E‐stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E‐stim appears to combine the relative strengths of each therapeutic. Repaired nerve injuries can fail to achieve functional recovery. We tested whether dual administration of FK506 and E‐stim further enhance regeneration and recovery. Two sets of rats nerve injury and repair models were measured for outcomes of early nerve regeneration and functional recovery. While dual administration of FK506 and E‐stim showed minimal additive effects compared to either therapy alone in regeneration or recovery, the concurrent use of both therapies ensured earlier functional recovery and decreased variability in outcomes.]]></description><identifier>ISSN: 0148-639X</identifier><identifier>EISSN: 1097-4598</identifier><identifier>DOI: 10.1002/mus.27748</identifier><identifier>PMID: 36333946</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>Animals ; Electric Stimulation ; electrical stimulation ; Electrical stimuli ; FK506 ; functional recovery ; Histology ; Immunosuppressive Agents - pharmacology ; Immunosuppressive Agents - therapeutic use ; Muscles ; Nerve Regeneration - physiology ; Nerves ; peripheral nerve ; Random Allocation ; Rats ; Recovery of function ; Recovery of Function - physiology ; Regeneration ; Stimulation ; Surgery ; Tacrolimus ; Tacrolimus - pharmacology ; Tacrolimus - therapeutic use ; Tibial nerve ; Tibial Nerve - pathology ; Walking</subject><ispartof>Muscle &amp; nerve, 2023-01, Vol.67 (1), p.78-87</ispartof><rights>2022 Wiley Periodicals LLC.</rights><rights>2023 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2838-40386ea176c2f2d86fe8d15055ec6678eb0460c2a1b27b2756cf06cb9d3f08c63</citedby><cites>FETCH-LOGICAL-c2838-40386ea176c2f2d86fe8d15055ec6678eb0460c2a1b27b2756cf06cb9d3f08c63</cites><orcidid>0000-0001-8132-6827 ; 0000-0002-9882-4213</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmus.27748$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmus.27748$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36333946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marsh, Evan B.</creatorcontrib><creatorcontrib>Schellhardt, Lauren</creatorcontrib><creatorcontrib>Hunter, Daniel A.</creatorcontrib><creatorcontrib>Mackinnon, Susan E.</creatorcontrib><creatorcontrib>Snyder‐Warwick, Alison K.</creatorcontrib><creatorcontrib>Wood, Matthew D.</creatorcontrib><title>Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes</title><title>Muscle &amp; nerve</title><addtitle>Muscle Nerve</addtitle><description><![CDATA[Introduction/Aims Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and recovery more than either therapeutic alone. Methods Rats were randomized to four groups: E‐stim, FK506, FK506 + E‐stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21‐ and 42‐day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. Results Dual E‐stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E‐stim, P < .05; FK506 + E‐stim, P < .05). The E‐stim and FK506 + E‐stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E‐stim, P < .05; FK506 + E‐stim, P < .01). The FK506 group had improved recovery based on walking‐track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit. Discussion Dual administration of FK506 and E‐stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E‐stim appears to combine the relative strengths of each therapeutic. Repaired nerve injuries can fail to achieve functional recovery. We tested whether dual administration of FK506 and E‐stim further enhance regeneration and recovery. Two sets of rats nerve injury and repair models were measured for outcomes of early nerve regeneration and functional recovery. While dual administration of FK506 and E‐stim showed minimal additive effects compared to either therapy alone in regeneration or recovery, the concurrent use of both therapies ensured earlier functional recovery and decreased variability in outcomes.]]></description><subject>Animals</subject><subject>Electric Stimulation</subject><subject>electrical stimulation</subject><subject>Electrical stimuli</subject><subject>FK506</subject><subject>functional recovery</subject><subject>Histology</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Muscles</subject><subject>Nerve Regeneration - physiology</subject><subject>Nerves</subject><subject>peripheral nerve</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Recovery of function</subject><subject>Recovery of Function - physiology</subject><subject>Regeneration</subject><subject>Stimulation</subject><subject>Surgery</subject><subject>Tacrolimus</subject><subject>Tacrolimus - pharmacology</subject><subject>Tacrolimus - therapeutic use</subject><subject>Tibial nerve</subject><subject>Tibial Nerve - pathology</subject><subject>Walking</subject><issn>0148-639X</issn><issn>1097-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9q3DAQh0VpabZpD32BIuglgTqRJVuSjyEkbWhCD22gNyPL410FW0r1Z8O-ZJ-pcrzJoRAQSPz45tMwg9DHkpyUhNDTKYUTKkQlX6FVSRpRVHUjX6MVKStZcNb8PkDvQrgjhJSSi7fogHHGWFPxFfp7MYKO3mg14hDNlEYVjbPYeRyV9m7MUcBHl99rwo-xGp0FDHajrIaALfgtYA9ryK-lTtk-B9ptwe-wGiL4PRWSX-fsC37YmBFwn_KHKczVfZpdW-XNbH00aDd1xuY0RA92HTcBuwGD0htsLL73bnLR2PVTJz12KeYaCO_Rm0GNAT7s70N0e3nx6_xbcf3j69X52XWhqWSyqAiTHFQpuKYD7SUfQPZlTeoaNOdCQkcqTjRVZUdFPjXXA-G6a3o2EKk5O0RHizf38idBiO1kgoZxVBZcCi0VjNaMVxXN6Of_0DuXvM3dtbOYECG4yNTxQuWZh-BhaO-9mZTftSVp5yW306M2Lzmzn_bG1E3QP5NPW83A6QI85FHvXja1N7c_F-U_J3O1Pw</recordid><startdate>202301</startdate><enddate>202301</enddate><creator>Marsh, Evan B.</creator><creator>Schellhardt, Lauren</creator><creator>Hunter, Daniel A.</creator><creator>Mackinnon, Susan E.</creator><creator>Snyder‐Warwick, Alison K.</creator><creator>Wood, Matthew D.</creator><general>John Wiley &amp; Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8132-6827</orcidid><orcidid>https://orcid.org/0000-0002-9882-4213</orcidid></search><sort><creationdate>202301</creationdate><title>Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes</title><author>Marsh, Evan B. ; Schellhardt, Lauren ; Hunter, Daniel A. ; Mackinnon, Susan E. ; Snyder‐Warwick, Alison K. ; Wood, Matthew D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2838-40386ea176c2f2d86fe8d15055ec6678eb0460c2a1b27b2756cf06cb9d3f08c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Electric Stimulation</topic><topic>electrical stimulation</topic><topic>Electrical stimuli</topic><topic>FK506</topic><topic>functional recovery</topic><topic>Histology</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Muscles</topic><topic>Nerve Regeneration - physiology</topic><topic>Nerves</topic><topic>peripheral nerve</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Recovery of function</topic><topic>Recovery of Function - physiology</topic><topic>Regeneration</topic><topic>Stimulation</topic><topic>Surgery</topic><topic>Tacrolimus</topic><topic>Tacrolimus - pharmacology</topic><topic>Tacrolimus - therapeutic use</topic><topic>Tibial nerve</topic><topic>Tibial Nerve - pathology</topic><topic>Walking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marsh, Evan B.</creatorcontrib><creatorcontrib>Schellhardt, Lauren</creatorcontrib><creatorcontrib>Hunter, Daniel A.</creatorcontrib><creatorcontrib>Mackinnon, Susan E.</creatorcontrib><creatorcontrib>Snyder‐Warwick, Alison K.</creatorcontrib><creatorcontrib>Wood, Matthew D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Muscle &amp; nerve</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marsh, Evan B.</au><au>Schellhardt, Lauren</au><au>Hunter, Daniel A.</au><au>Mackinnon, Susan E.</au><au>Snyder‐Warwick, Alison K.</au><au>Wood, Matthew D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes</atitle><jtitle>Muscle &amp; nerve</jtitle><addtitle>Muscle Nerve</addtitle><date>2023-01</date><risdate>2023</risdate><volume>67</volume><issue>1</issue><spage>78</spage><epage>87</epage><pages>78-87</pages><issn>0148-639X</issn><eissn>1097-4598</eissn><abstract><![CDATA[Introduction/Aims Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E‐stim), can improve recovery. We tested whether dual administration of FK506 and E‐stim enhances regeneration and recovery more than either therapeutic alone. Methods Rats were randomized to four groups: E‐stim, FK506, FK506 + E‐stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21‐ and 42‐day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. Results Dual E‐stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E‐stim, P < .05; FK506 + E‐stim, P < .05). The E‐stim and FK506 + E‐stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E‐stim, P < .05; FK506 + E‐stim, P < .01). The FK506 group had improved recovery based on walking‐track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit. Discussion Dual administration of FK506 and E‐stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E‐stim appears to combine the relative strengths of each therapeutic. Repaired nerve injuries can fail to achieve functional recovery. We tested whether dual administration of FK506 and E‐stim further enhance regeneration and recovery. Two sets of rats nerve injury and repair models were measured for outcomes of early nerve regeneration and functional recovery. While dual administration of FK506 and E‐stim showed minimal additive effects compared to either therapy alone in regeneration or recovery, the concurrent use of both therapies ensured earlier functional recovery and decreased variability in outcomes.]]></abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>36333946</pmid><doi>10.1002/mus.27748</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8132-6827</orcidid><orcidid>https://orcid.org/0000-0002-9882-4213</orcidid></addata></record>
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subjects Animals
Electric Stimulation
electrical stimulation
Electrical stimuli
FK506
functional recovery
Histology
Immunosuppressive Agents - pharmacology
Immunosuppressive Agents - therapeutic use
Muscles
Nerve Regeneration - physiology
Nerves
peripheral nerve
Random Allocation
Rats
Recovery of function
Recovery of Function - physiology
Regeneration
Stimulation
Surgery
Tacrolimus
Tacrolimus - pharmacology
Tacrolimus - therapeutic use
Tibial nerve
Tibial Nerve - pathology
Walking
title Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes
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