{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T21:56:49Z","timestamp":1759010209348,"version":"3.41.2"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Local therapeutic hypothermia (32\u00b0C) has been linked experimentally to an otoprotective effect in the electrode insertion trauma. The pathomechanism of the electrode insertion trauma is connected to the activation of apoptosis and necrosis pathways, pro-inflammatory and fibrotic mechanisms. In a whole organ cochlea culture setting the effect of therapeutic hypothermia in an electrode insertion trauma model is evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>The cochleae of C57Bl6\/J mice (Charles River\u00ae, Freiburg, Germany) are cultured for 24 hours at 37\u00b0C and 32\u00b0C after inserting a fishing line through the round window simulating an insertion trauma. The resulting effect was evaluated for the apoptotic reaction \u2013 B-cell-Lymphoma-2-Associated-X-Protein (BAX), B-Cell-Lymphoma-2-Protein (BCL2) and Cleaved-Caspase-3 (CC3) \u2013, the inflammatory response \u2013 Tumor-Necrosis-Factor-Alpha (TNF\u03b1), Interleukin-1-Beta (IL-1Imm) and Cyclooxygenase-2 (COX2) \u2013 and proliferation process \u2013 Transforming-Growth-Factor-Beta-1 (TGF\u03b21) \u2013 using immunohistochemistry and real-time PCR technique. A minimum of 12 cochlea per experiment were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A pro-apoptotic situation was observed in the normothermic group (BAX, CC3 \u02c3 Bcl2) whereas an anti-apoptotic constellation was found at 32\u00b0C culture conditions (BAX, CC3 &amp;lt; Bcl2). Furthermore the effect of the IT knowing to effect the pro-inflammatory cytokine (TNF\u03b1, Il1\u03b2) and enzyme (COX2) expression has been reproduced. This reaction was reversed with the application of therapeutic hypothermia resulting in significant lower pro-inflammatory cytokine (TNF\u03b1, Il1\u03b2) and enzyme (COX2) expression. TGF\u03b21 was increased by hypothermia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1112243","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T04:30:17Z","timestamp":1681360217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture"],"prefix":"10.3389","volume":"17","author":[{"given":"Joachim","family":"Schmutzhard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Bader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Gottfried","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Dejaco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Gl\u00fcckert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joszef","family":"Dudas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"Schrott-Fischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1089\/ten.tec.2009.0028","article-title":"A novel buoyancy technique optimizes simulated microgravity conditions for whole sensory organ culture in rotating bioreactors","volume":"16","author":"Arnold","year":"2010","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"620691","DOI":"10.3389\/fneur.2020.620691","article-title":"Measurement of the Intracochlear hypothermia distribution utilizing tympanic cavity hypothermic rinsing technique in a cochlea hypothermia model","volume":"11","author":"Bader","year":"2020","journal-title":"Front. Neurol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1097\/01.mlg.0000173169.45262.ae","article-title":"Mild hypothermia protects auditory function during cochlear implant surgery","volume":"115","author":"Balkany","year":"2005","journal-title":"Laryngoscope"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1002\/ar.22585","article-title":"A novel organ of corti explant model for the study of cochlear implantation trauma","volume":"295","author":"Bas","year":"2012","journal-title":"Anat. Rec."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev.immunol.16.1.395","article-title":"BCL-2 family: regulators of cell death","volume":"16","author":"Chao","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jneumeth.2008.09.007","article-title":"A protocol for cryoembedding the adult Guinea pig cochlea for fluorescence immunohistology","volume":"176","author":"Coleman","year":"2009","journal-title":"J. Neurosci. Methods"},{"key":"ref7","doi-asserted-by":"publisher","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":"Eshraghi","year":"2007","journal-title":"Otol. Neurotol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"492","DOI":"10.3389\/fncel.2019.00492","article-title":"Otoprotection to implanted cochlea exposed to noise trauma with dexamethasone eluting electrode","volume":"13","author":"Eshraghi","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1097\/00005537-200303000-00005","article-title":"Comparative study of cochlear damage with three perimodiolar electrode designs","volume":"113","author":"Eshraghi","year":"2003","journal-title":"Laryngoscope"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.21053\/ceo.2021.00920","article-title":"Cytokines and inflammation in Meniere disease","volume":"15","author":"Frejo","year":"2022","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jneumeth.2008.02.004","article-title":"Whole organ culture of the postnatal sensory inner ear in simulated microgravity","volume":"171","author":"Hahn","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.2174\/157015912799362751","article-title":"Molecular and cellular pathways as a target of therapeutic hypothermia: pharmacological aspect","volume":"10","author":"Han","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0378-5955(84)90111-4","article-title":"Hypothermia protects the cochlea from noise damage","volume":"16","author":"Henry","year":"1984","journal-title":"Hear. Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/rheumatology\/keq031","article-title":"Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents","volume":"49","author":"Horiuchi","year":"2010","journal-title":"Rheumatology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1177\/000348941312200107","article-title":"Molecular and cellular mechanisms of loss of residual hearing after cochlear implantation","volume":"122","author":"Jia","year":"2013","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref01","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12861-019-0191-y","article-title":"Growth and cellular patterning during fetal human inner ear development studied by a correlative imaging approach","volume":"19","author":"Johnson Chacko","year":"2019","journal-title":"BMC Dev. Biol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4103\/1673-5374.202915","article-title":"Neuroprotective mechanisms and translational potential of therapeutic hypothermia in the treatment of ischemic stroke","volume":"12","author":"Lee","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3892\/etm.2022.11147","article-title":"Effect of intravenous thrombolysis combined with mild hypothermia on the levels of IL-1beta, IL-6, ICAM-1 and MMP-2 in patients with acute cerebral infarction and clinical significance","volume":"23","author":"Li","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2746","DOI":"10.1523\/JNEUROSCI.17-08-02746.1997","article-title":"Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage","volume":"17","author":"Nogawa","year":"1997","journal-title":"J. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/labinvest.3700669","article-title":"Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations","volume":"87","author":"Prud\u2019homme","year":"2007","journal-title":"Lab. Investig."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s00418-015-1350-2","article-title":"Spatio-temporal dynamics of beta-tubulin isotypes during the development of the sensory auditory organ in rat","volume":"144","author":"Renauld","year":"2015","journal-title":"Histochem. Cell Biol."},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169229","article-title":"Mild therapeutic hypothermia protects from acute and chronic renal ischemia-reperfusion injury in mice by mitigated mitochondrial dysfunction and modulation of local and systemic inflammation","volume":"23","author":"Schleef","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032013","article-title":"Closing the gap between the auditory nerve and Cochlear implant electrodes: which Neurotrophin cocktail performs best for axonal outgrowth and is electrical stimulation beneficial?","volume":"24","author":"Schmidbauer","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/00016480600794487","article-title":"Induction of localized cochlear hypothermia","volume":"127","author":"Smith","year":"2007","journal-title":"Acta Otolaryngol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.heares.2015.11.009","article-title":"Assessment of thermal treatment via irrigation of external ear to reduce cisplatin-induced hearing loss","volume":"332","author":"Spankovich","year":"2016","journal-title":"Hear. Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1089\/ars.2021.0184","article-title":"Mild therapeutic hypothermia and putative mechanisms of hair cell survival in the cochlea","volume":"36","author":"Spankovich","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref02","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/00016488709124973","article-title":"The block surface method for evaluation of human inner ears","volume":"436","author":"Spoendlin","year":"1987","journal-title":"Acta. Otolaryngol. Suppl."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.heares.2016.05.015","article-title":"A cool approach to reducing electrode-induced trauma: localized therapeutic hypothermia conserves residual hearing in cochlear implantation","volume":"339","author":"Tamames","year":"2016","journal-title":"Hear. Res."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/S0306-4522(00)00510-8","article-title":"Hypothermia prevents hearing loss and progressive hair cell loss after transient cochlear ischemia in gerbils","volume":"102","author":"Watanabe","year":"2001","journal-title":"Neuroscience"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"cm1","DOI":"10.1126\/scisignal.3105cm1","article-title":"Interleukin-1 (IL-1) pathway","volume":"3","author":"Weber","year":"2010","journal-title":"Sci. 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