{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:24:40Z","timestamp":1793060680201,"version":"4.5.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Severe axonal damage in the peripheral nerves results in retrograde degeneration towards the central side, leading to neuronal cell death, eventually resulting in incomplete axonal regeneration and functional recovery. Therefore, it is necessary to evaluate the facial nerve nucleus in models of facial paralysis, and investigate the efficacy of treatments, to identify treatment options for severe paralysis. Consequently, we aimed to examine the percentage of facial nerve cell reduction and the extent to which intratympanic administration of a basic fibroblast growth factor (bFGF) inhibits neuronal cell death in a model of severe facial paralysis. A severe facial paralysis model was induced in Hartley guinea pigs by freezing the facial canal. Animals were divided into two groups: one group was treated with gelatin hydrogel impregnated with bFGF (bFGF group) and the other was treated with gelatin hydrogel impregnated with saline (control group). Facial movement scoring, electrophysiological testing, and histological assessment of facial neurons were performed. The freezing-induced facial paralysis model showed a facial neuronal cell death rate of 29.0%; however, bFGF administration reduced neuronal cell death to 15.8%. Facial movement scores improved in the bFGF group compared with those in the control group. Intratympanic bFGF administration has a protective effect on facial neurons in a model of severe facial paralysis. These findings suggest a potential therapeutic approach for treating patients with refractory facial paralysis. Further studies are required to explore the clinical applicability of this treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0312357","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T13:34:17Z","timestamp":1738848857000},"page":"e0312357","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Basic fibroblast growth factor helps protect facial nerve cells in a freeze-induced paralysis model"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3956-1539","authenticated-orcid":true,"given":"Shinji","family":"Iwata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Teraoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takemichi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Joko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Tabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Wakisaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohito","family":"Hato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"issue":"7","key":"pone.0312357.ref001","doi-asserted-by":"crossref","first-page":"E283","DOI":"10.1002\/lary.24542","article-title":"Etiology, diagnosis, and management of facial palsy: 2000 patients at a facial nerve center","volume":"124","author":"MH Hohman","year":"2014","journal-title":"Laryngoscope"},{"issue":"3","key":"pone.0312357.ref002","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bjorl.2016.03.016","article-title":"The role of facial canal diameter in the pathogenesis and grade of Bell\u2019s palsy: a study by high resolution computed tomography.","volume":"83","author":"O Celik","year":"2017","journal-title":"Braz J Otorhinolaryngol."},{"issue":"1","key":"pone.0312357.ref003","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3109\/00016480902896139","article-title":"Basic fibroblast growth factor combined with biodegradable hydrogel promotes healing of facial nerve after compression injury: an experimental study.","volume":"130","author":"H Komobuchi","year":"2010","journal-title":"Acta Otolaryngol."},{"issue":"4","key":"pone.0312357.ref004","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/0194599811431661","article-title":"Facial nerve decompression surgery using bFGF-impregnated biodegradable gelatin hydrogel in patients with Bell palsy","volume":"146","author":"N Hato","year":"2012","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"4","key":"pone.0312357.ref005","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/BF00186909","article-title":"Quantitative analysis of the retrograde reaction of motoneurons with an image analyser","volume":"181","author":"FH Rauch","year":"1990","journal-title":"Anat Embryol (Berl)."},{"issue":"5","key":"pone.0312357.ref006","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0361-9230(98)00178-6","article-title":"Extensive neuronal cell death following intracranial transection of the facial nerve in the adult rat","volume":"49","author":"P Mattsson","year":"1999","journal-title":"Brain Res Bull"},{"issue":"11","key":"pone.0312357.ref007","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1002\/lary.21077","article-title":"Facial motor nuclei cell loss with intratemporal facial nerve crush injuries in rats","volume":"120","author":"SJ Marzo","year":"2010","journal-title":"Laryngoscope"},{"issue":"19","key":"pone.0312357.ref008","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1073\/pnas.83.19.7537","article-title":"Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture","volume":"83","author":"RS Morrison","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0312357.ref009","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1073\/pnas.83.9.3012","article-title":"Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension","volume":"83","author":"P Walicke","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0312357.ref010","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1177\/0271678X20943823","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"40","author":"N Percie du Sert","year":"2020","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"pone.0312357.ref011","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.anl.2020.03.012","article-title":"Non-recovery animal model of severe facial paralysis induced by freezing the facial canal.","volume":"47","author":"T Joko","year":"2020","journal-title":"Auris Nasus Larynx"},{"issue":"1","key":"pone.0312357.ref012","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1163\/156856299X00298","article-title":"Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor","volume":"10","author":"Y Tabata","year":"1999","journal-title":"J Biomater Sci Polym Ed"},{"issue":"15","key":"pone.0312357.ref013","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1523\/JNEUROSCI.20-15-05587.2000","article-title":"Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus","volume":"20","author":"AF Hottinger","year":"2000","journal-title":"J Neurosci"},{"key":"pone.0312357.ref014","volume-title":"Contemporary Research methods in neuroanatomy.","author":"Springer","year":"1970"},{"issue":"3","key":"pone.0312357.ref015","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/00129492-200205000-00029","article-title":"Apoptosis and expression of BCL-2 in facial motoneurons after facial nerve injury","volume":"23","author":"ZM Wang","year":"2002","journal-title":"Otol Neurotol"},{"key":"pone.0312357.ref016","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1016\/j.wneu.2017.09.157","article-title":"Acute response of neurons: an early event of neuronal cell death after facial nerve injury","volume":"109","author":"Z Sun","year":"2018","journal-title":"World Neurosurg"},{"key":"pone.0312357.ref017","doi-asserted-by":"crossref","first-page":"e02145","DOI":"10.1128\/mBio.02145-15","article-title":"Two modes of the axonal interferon response limit alphaherpesvirus neuroinvasion.","volume":"7","author":"R Song","year":"2016","journal-title":"mBio."},{"issue":"1","key":"pone.0312357.ref018","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3390\/ijms13011225","article-title":"Disruption of axonal transport in motor neuron diseases","volume":"13","author":"K Ikenaka","year":"2012","journal-title":"Int J Mol Sci"},{"issue":"4 Pt 1","key":"pone.0312357.ref019","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1177\/000348947708600416","article-title":"Pathogenesis of Bell\u2019s palsy. Retrograde epineurial edema and postedematous fibrous compression neuropathy of the facial nerve.","volume":"86","author":"R. Gussen","year":"1977","journal-title":"Ann Otol Rhinol Laryngol."},{"issue":"6","key":"pone.0312357.ref020","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3109\/00016486709128786","article-title":"Herpes zoster auris associated with facial nerve palsy and auditory nerve symptoms: a case report with histopathological findings.","volume":"63","author":"B Blackley","year":"1967","journal-title":"Acta Otolaryngol"},{"key":"pone.0312357.ref021","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3389\/fphys.2018.01519","article-title":"Peripheral nerve injury induces dynamic changes of tight junction components.","volume":"9","author":"X Wang","year":"2018","journal-title":"Front Physiol"},{"issue":"11","key":"pone.0312357.ref022","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1177\/000348949210101108","article-title":"Facial canal dehiscence: histologic study and computer reconstruction","volume":"101","author":"H Takahashi","year":"1992","journal-title":"Ann Otol Rhinol Laryngol"},{"issue":"3 Pt 1","key":"pone.0312357.ref023","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1288\/00005537-199403000-00012","article-title":"Prevalence of facial canal dehiscence and of persistent stapedial artery in the human middle ear: a report of 1000 temporal bones","volume":"104","author":"EH Moreano","year":"1994","journal-title":"Laryngoscope"},{"issue":"1","key":"pone.0312357.ref024","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/01.CIR.91.1.145","article-title":"Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart","volume":"91","author":"DF Lazarous","year":"1995","journal-title":"Circulation"},{"key":"pone.0312357.ref025","volume-title":"StatPearls","author":"J Casale","year":"2024"},{"key":"pone.0312357.ref026","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0168-3659(94)00035-2","article-title":"Enhanced vascularization and tissue granulation by basic fibroblast growth factor impregnated in gelatin hydrogels","volume":"31","author":"Y Tabata","year":"1994","journal-title":"J Control Release"},{"issue":"1","key":"pone.0312357.ref027","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0196-0709(00)80084-8","article-title":"Study on facial motoneuronal death after proximal or distal facial nerve transection.","volume":"21","author":"CF Dai","year":"2000","journal-title":"Am J Otol"},{"issue":"1\u20132","key":"pone.0312357.ref028","first-page":"67","article-title":"The cellular and molecular basis of peripheral nerve regeneration","volume":"14","author":"SY Fu","year":"1997","journal-title":"Mol Neurobiol"},{"issue":"4","key":"pone.0312357.ref029","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3950\/jibiinkoka.79.491","article-title":"Morphological change in the nuclear cells after sectioning the facial nerve of rabbit.","volume":"79","author":"A. Nomura","year":"1976","journal-title":"Nippon Jibiinkoka Gakkai Kaiho (in Japanese)."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T13:34:37Z","timestamp":1738848877000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312357"}},"subtitle":[],"editor":[{"given":"Christophe","family":"Egles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0312357","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.08.617179","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}