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As nerves are typically intact at a procedure\u2019s completion, paresis is hypothesized to result from a combination of neurapraxia and axonotmesis. As both neurapraxia and axonotmesis involve Schwann cell injury and require remyelination, we developed an in vitro RSC96 Schwann cell model of injury using hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) to induce oxidative stress and investigated the efficacy of candidate therapeutic agents to promote RSC96 viability. As a first step in developing a long-term local administration strategy, the most promising of these agents was incorporated into sustained-release microparticles and investigated for bioactivity using this assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The concentration of H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      which reduced viability by 50% was determined to establish a standard for inducing oxidative stress in RSC96 cultures. Fresh cultures were then co-dosed with H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      and the potential therapeutics melatonin,\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine, resveratrol, and 4-aminopyridine. Schwann cell viability was evaluated and the most efficacious agent,\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine, was encapsulated into microparticles. Eluted samples of\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine from microparticles was evaluated for retained bioactivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      100\u00a0\u00b5M\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine improved the viability of Schwann cells dosed with H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . 100\u00a0\u00b5M Microparticle-eluted\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine also enhanced Schwann cell viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We developed a Schwann cell culture model of iatrogenic nerve injury and used this to identify\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine as an agent to promote recovery.\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine was packaged into microparticles and demonstrated promise as a locally administrable agent to reduce oxidative stress in Schwann cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00405-024-08622-z","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T23:50:51Z","timestamp":1713829851000},"page":"3805-3812","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An in vitro model for postoperative cranial nerve dysfunction and a proposed method of rehabilitation with N-acetylcysteine microparticles"],"prefix":"10.1007","volume":"281","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-8271","authenticated-orcid":false,"given":"Ashley","family":"Kita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Kedeshian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"issue":"10","key":"8622_CR1","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1080\/00016480600672618","volume":"126","author":"O Guntinas-Lichius","year":"2006","unstructured":"Guntinas-Lichius O, Gabriel B, Klussmann JP (2006) Risk of facial palsy and severe Frey\u2019s syndrome after conservative parotidectomy for benign disease: analysis of 610 operations. 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