{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:43:39Z","timestamp":1787499819563,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E\u2010stim), can improve recovery. We tested whether dual administration of FK506 and E\u2010stim enhances regeneration and recovery more than either therapeutic alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were randomized to four groups: E\u2010stim, FK506, FK506\u2009+\u2009E\u2010stim, 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\u00a0=\u00a036) and functional recovery (n\u00a0=\u00a042) (21\u2010 and 42\u2010day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dual E\u2010stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.0001; E\u2010stim,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05; FK506\u2009+\u2009E\u2010stim,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05). The E\u2010stim and FK506\u2009+\u2009E\u2010stim groups had improved behavioral recovery compared with repair alone (at 6\u2009weeks: E\u2010stim,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05; FK506\u2009+\u2009E\u2010stim,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.01). The FK506 group had improved recovery based on walking\u2010track analysis (at 6\u2009weeks:\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) and muscle force and mass (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05). 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Dual administration of FK506 and E\u2010stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E\u2010stim appears to combine the relative strengths of each therapeutic.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.27748","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T03:40:48Z","timestamp":1667619648000},"page":"78-87","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Electrical stimulation or tacrolimus (\n                    <scp>FK506<\/scp>\n                    ) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes"],"prefix":"10.1002","volume":"67","author":[{"given":"Evan B.","family":"Marsh","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine  St. Louis 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K.","family":"Snyder\u2010Warwick","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-6827","authenticated-orcid":false,"given":"Matthew D.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine  St. Louis 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