{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:36:52Z","timestamp":1790530612788,"version":"4.1.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Community 6th Framework Programme","award":["26556"],"award-info":[{"award-number":["26556"]}]},{"name":"European Community 5th Framework Programme","award":["QLG3-CT-2002-01563"],"award-info":[{"award-number":["QLG3-CT-2002-01563"]}]},{"name":"European Community 7th Framework Programme","award":["304930"],"award-info":[{"award-number":["304930"]}]},{"name":"European Community FP7 Post-Grant Open Access Pilot"},{"name":"MED-EL Innsbruck"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0183820","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T13:34:23Z","timestamp":1504186463000},"page":"e0183820","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Local inner ear application of dexamethasone in cochlear implant models is safe for auditory neurons and increases the neuroprotective effect of chronic electrical stimulation"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8618-8793","authenticated-orcid":true,"given":"Verena","family":"Scheper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Hessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"H\u00fctten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Wilk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Jolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lenarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Paasche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,8,31]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"925485","DOI":"10.1155\/2014\/925485","article-title":"Prevention and restoration of hearing loss associated with the use of cisplatin","volume":"2014","author":"F Chirtes","year":"2014","journal-title":"Biomed Res Int"},{"issue":"3","key":"ref2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.amjoto.2015.12.007","article-title":"Treatment of Meniere&apos;s disease with intratympanic dexamethazone plus high dosage of betahistine","volume":"37","author":"S Albu","year":"2016","journal-title":"American journal of otolaryngology"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5152\/iao.2016.2177","article-title":"Response Over Time of Vertigo Spells to Intratympanic Dexamethasone Treatment in Meniere&apos;s Disease Patients","volume":"12","author":"N Atrache Al Attrache","year":"2016","journal-title":"The journal of international advanced otology"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000445774","article-title":"Tinnitus: Evaluation of Intratympanic Injection of Combined Lidocaine and Corticosteroids","volume":"78","author":"S Elzayat","year":"2016","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/lary.20074","article-title":"Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy","volume":"119","author":"SK Plontke","year":"2009","journal-title":"The Laryngoscope"},{"issue":"6","key":"ref6","first-page":"1431","article-title":"Effectiveness of intratympanic dexamethasone for refractory sudden sensorineural hearing loss","volume":"271","author":"O Erdur","year":"2014","journal-title":"European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-Laryngology\u2014Head and Neck Surgery"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"e0147552","DOI":"10.1371\/journal.pone.0147552","article-title":"Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode","volume":"11","author":"M Wilk","year":"2016","journal-title":"PloS one"},{"issue":"8","key":"ref8","doi-asserted-by":"crossref","first-page":"e104564","DOI":"10.1371\/journal.pone.0104564","article-title":"In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment","volume":"9","author":"M H\u00fctten","year":"2014","journal-title":"PloS one"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1097\/MAO.0b013e31805778fc","article-title":"Local dexamethasone therapy conserves hearing in an animal model of electrode insertion trauma-induced hearing loss","volume":"28","author":"AA Eshraghi","year":"2007","journal-title":"Otol Neurotol"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000329791","article-title":"Protection of inner ear function after cochlear implantation: compound action potential measurements after local application of glucocorticoids in the guinea pig cochlea","volume":"73","author":"S Braun","year":"2011","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000314757","article-title":"Pre-operative intravenous dexamethasone prevents auditory threshold shift in a guinea pig model of cochlear implantation","volume":"16","author":"TM Connolly","year":"2011","journal-title":"Audiology & neuro-otology"},{"key":"ref12","first-page":"423","article-title":"Free Radicals in ENT Pathology","author":"T Lenarz","year":"2015"},{"issue":"2","key":"ref13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10162-013-0440-x","article-title":"Auditory-nerve responses to varied inter-phase gap and phase duration of the electric pulse stimulus as predictors for neuronal degeneration","volume":"15","author":"D Ramekers","year":"2014","journal-title":"Journal of the Association for Research in Otolaryngology: JARO"},{"issue":"1\u20133","key":"ref14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0378-5955(90)90102-U","article-title":"Estimation of surviving spiral ganglion cells in the deaf rat using the electrically evoked auditory brainstem response","volume":"49","author":"RD Hall","year":"1990","journal-title":"Hear Res"},{"issue":"8","key":"ref15","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1097\/01.mlg.0000227176.09500.28","article-title":"Multichannel cochlear implants: relation of histopathology to performance","volume":"116","author":"JN Fayad","year":"2006","journal-title":"The Laryngoscope"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3109\/00016489.2011.647361","article-title":"Multi-channel cochlear implant histopathology: are fewer spiral ganglion cells really related to better clinical performance?","volume":"132","author":"HX Xu","year":"2012","journal-title":"Acta Oto-Laryngol"},{"issue":"10","key":"ref17","doi-asserted-by":"crossref","first-page":"764","DOI":"10.7326\/0003-4819-141-10-200411160-00007","article-title":"Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease","volume":"141","author":"L Wei","year":"2004","journal-title":"Ann Intern Med"},{"issue":"11","key":"ref18","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1136\/annrheumdis-2012-202021","article-title":"Understanding the side effects of glucocorticoid therapy: shining a light on a drug everyone thinks they know","volume":"71","author":"WG Dixon","year":"2012","journal-title":"Annals of the rheumatic diseases"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/MAO.0b013e3181d2796c","article-title":"Intratympanic steroid prevents long-term spiral ganglion neuron loss in experimental meningitis","volume":"31","author":"L Worsoe","year":"2010","journal-title":"Otol Neurotol"},{"issue":"6","key":"ref20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1159\/000241897","article-title":"Targeted therapy of the inner ear","volume":"14","author":"S Maini","year":"2009","journal-title":"Audiology & neuro-otology"},{"issue":"7","key":"ref21","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1097\/MAO.0b013e318263d35d","article-title":"A randomized, double-blind, placebo-controlled clinical study to assess safety and clinical activity of OTO-104 given as a single intratympanic injection in patients with unilateral Meniere&apos;s disease","volume":"33","author":"PR Lambert","year":"2012","journal-title":"Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.heares.2015.04.019","article-title":"Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study","volume":"327","author":"Y Liu","year":"2015","journal-title":"Hearing Research"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1179\/1754762813Y.0000000054","article-title":"Development of a safe dexamethasone-eluting electrode array for cochlear implantation","volume":"15","author":"D Stathopoulos","year":"2014","journal-title":"Cochlear Implants International"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.heares.2015.06.010","article-title":"The role of extended preoperative steroids in hearing preservation cochlear implantation","volume":"327","author":"J Kuthubutheen","year":"2015","journal-title":"Hear Res"},{"issue":"6","key":"ref25","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/jnr.21964","article-title":"Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs","volume":"87","author":"V Scheper","year":"2009","journal-title":"J Neurosci Res"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/cne.10480","article-title":"Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation","volume":"454","author":"S Kanzaki","year":"2002","journal-title":"J Comp Neurol"},{"issue":"1\u20132","key":"ref27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0378-5955(96)00202-X","article-title":"Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig","volume":"105","author":"A Mitchell","year":"1997","journal-title":"Hear Res"},{"key":"ref28","first-page":"2449","article-title":"Lipidic nanocapsule drug delivery: neuronal protection for cochlear implant optimization","volume":"7","author":"H Meyer","year":"2012","journal-title":"International journal of nanomedicine"},{"key":"ref29","article-title":"Development of a Polymeric Coating for Cochlear Implant Electrodes to Deliver Dexamethasone into the Inner Ear [experimental]","author":"P Ceschi","year":"2013"},{"issue":"2","key":"ref30","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.nbd.2006.09.012","article-title":"Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs","volume":"25","author":"J Maruyama","year":"2007","journal-title":"Neurobiol Dis"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.heares.2013.08.002","article-title":"Spiral ganglion neuron quantification in the guinea pig cochlea using Confocal Laser Scanning Microscopy compared to embedding methods","volume":"306","author":"A Wrzeszcz","year":"2013","journal-title":"Hearing Research"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/jnr.20239","article-title":"Delayed neurotrophic treatment preserves nerve survival and electrophysiological responsiveness in neomycin-deafened guinea pigs","volume":"78","author":"T Yamagata","year":"2004","journal-title":"J Neurosci Res"},{"key":"ref33","article-title":"Glukokortikoide bei obstruktiven Atemwegserkrankungen: Eine aktuelle Bestandsaufnahme","author":"HL Hahn","year":"1990"},{"issue":"8","key":"ref34","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1288\/00005537-199308000-00007","article-title":"Localization of glucocorticoid receptors and glucocorticoid receptor mRNAs in the rat cochlea","volume":"103","author":"WJ ten Cate","year":"1993","journal-title":"The Laryngoscope"},{"issue":"1","key":"ref35","doi-asserted-by":"crossref","first-page":"E29","DOI":"10.1002\/lary.25345","article-title":"Dexamethasone prevents hearing loss by restoring glucocorticoid receptor expression in the guinea pig cochlea","volume":"126","author":"UR Heinrich","year":"2016","journal-title":"The Laryngoscope"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1179\/1754762813Y.0000000053","article-title":"Dexamethasone eluting electrodes for cochlear implantation: Effect on residual hearing","volume":"16","author":"D Douchement","year":"2015","journal-title":"Cochlear Implants International"},{"issue":"2","key":"ref37","first-page":"230","article-title":"Effect of transtympanic injection of steroids on cochlear blood flow, auditory sensitivity, and histology in the guinea pig","volume":"19","author":"NA Shirwany","year":"1998","journal-title":"The American journal of otology"},{"issue":"11","key":"ref38","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1097\/MLG.0b013e31818173ec","article-title":"Dexamethasone base conserves hearing from electrode trauma-induced hearing loss","volume":"118","author":"RJ Vivero","year":"2008","journal-title":"The Laryngoscope"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.heares.2016.02.003","article-title":"Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study","volume":"337","author":"E Bas","year":"2016","journal-title":"Hear Res"},{"issue":"18","key":"ref40","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1097\/00001756-200512190-00008","article-title":"Brain-derived neurotrophic factor\/glial cell line-derived neurotrophic factor survival effects on auditory neurons are not limited by dexamethasone","volume":"16","author":"P Wefstaedt","year":"2005","journal-title":"Neuroreport"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/MAO.0b013e3182009d29","article-title":"OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders","volume":"32","author":"F Piu","year":"2011","journal-title":"Otol Neurotol"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10162-013-0372-5","article-title":"Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on survival and function of cochlear spiral ganglion neurons in deafened, developing cats","volume":"14","author":"PA Leake","year":"2013","journal-title":"J Assoc Res Otolaryngol"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/(SICI)1096-9861(19991004)412:4<543::AID-CNE1>3.0.CO;2-3","article-title":"Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness","volume":"412","author":"PA Leake","year":"1999","journal-title":"J Comp Neurol"},{"key":"ref44","first-page":"57","article-title":"Effectiveness of different electrical stimulation conditions in preservation of spiral ganglion cells following deafness","volume":"166","author":"JM Miller","year":"1995","journal-title":"Ann Otol Rhinol Laryngol Suppl"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0378-5955(91)90120-X","article-title":"Chronic intracochlear electrical stimulation induces selective survival of spiral ganglion neurons in neonatally deafened cats","volume":"54","author":"PA Leake","year":"1991","journal-title":"Hear Res"},{"issue":"1\u20132","key":"ref46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.heares.2007.12.005","article-title":"Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss","volume":"242","author":"RK Shepherd","year":"2008","journal-title":"Hear Res"},{"issue":"6","key":"ref47","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1523\/JNEUROSCI.17-06-01959.1997","article-title":"Trophic support of cultured spiral ganglion neurons by depolarization exceeds and is additive with that by neurotrophins or cAMP and requires elevation of [Ca2+]i within a set range","volume":"17","author":"JL Hegarty","year":"1997","journal-title":"J Neurosci"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0006-8993(02)04170-7","article-title":"Mechanism of electrical stimulation-induced neuroprotection: effects of verapamil on protection of primary auditory afferents","volume":"966","author":"AL Miller","year":"2003","journal-title":"Brain Res"},{"issue":"7","key":"ref49","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1523\/JNEUROSCI.21-07-02256.2001","article-title":"Multiple distinct signal pathways, including an autocrine neurotrophic mechanism, contribute to the survival-promoting effect of depolarization on spiral ganglion neurons in vitro","volume":"21","author":"MR Hansen","year":"2001","journal-title":"J Neurosci"},{"issue":"5","key":"ref50","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/01.moo.0000180919.68812.b9","article-title":"Strategies to preserve or regenerate spiral ganglion neurons","volume":"13","author":"PC Roehm","year":"2005","journal-title":"Curr Opin Otolaryngol Head Neck Surg"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(96)00193-1","article-title":"Chronic electrical stimulation of the auditory nerve at high stimulus rates: A physiological and histopathological study","volume":"105","author":"J Xu","year":"1997","journal-title":"Hearing Research"},{"issue":"2","key":"ref52","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/ejp.544","article-title":"Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity","volume":"19","author":"DB Bas","year":"2015","journal-title":"Eur J Pain"},{"issue":"5","key":"ref53","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/01.moo.0000186335.44206.1c","article-title":"The basic science of Meniere&apos;s disease and endolymphatic hydrops","volume":"13","author":"MT Semaan","year":"2005","journal-title":"Current opinion in otolaryngology & head and neck surgery"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.heares.2017.04.013","article-title":"Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea","volume":"350","author":"WS Konerding","year":"2017","journal-title":"Hearing Research"},{"issue":"4","key":"ref55","doi-asserted-by":"crossref","first-page":"E149","DOI":"10.1002\/lary.25011","article-title":"Evaluation of the selective glucocorticoid receptor agonist compound A for ototoxic effects","volume":"125","author":"C Honeder","year":"2015","journal-title":"The Laryngoscope"},{"issue":"1","key":"ref56","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/2277-9175.184277","article-title":"Intratympanic dexamethasone injection vs methylprednisolone for the treatment of refractory sudden sensorineural hearing loss","volume":"5","author":"N Berjis","year":"2016","journal-title":"Advanced Biomedical Research"},{"issue":"1","key":"ref57","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/lary.22142","article-title":"The role of preoperative, intratympanic glucocorticoids for hearing preservation in cochlear implantation: a prospective clinical study","volume":"122","author":"GP Rajan","year":"2012","journal-title":"The Laryngoscope"},{"issue":"4","key":"ref58","first-page":"564","article-title":"Intratympanic injection of dexamethasone: time course of inner ear distribution and conversion to its active form","volume":"27","author":"CA Hargunani","year":"2006","journal-title":"Otol Neurotol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0183820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T20:39:54Z","timestamp":1570048794000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0183820"}},"subtitle":[],"editor":[{"given":"Yann","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,8,31]]},"references-count":58,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0183820","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,31]]}}}