The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture

Frontiers in Neuroscience

Neuroscience

Annelies Schrott-Fischer¹  Timo Gottfried¹  Joszef Dudas¹  Werner Bader¹  Rudolf Glückert¹  Daniel Dejaco¹  Joachim Schmutzhard² 

[1]Department for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, Innsbruck, Austria

[2]null

关键词: hypothermia;    whole organ cochlea culture;    electrode insertion trauma;    cochlear implant;    sensorineural hearing loss;    hearing rehabilitation;   

DOI  :  10.3389/fnins.2023.1112243

 received in 2022-11-30, accepted in 2023-03-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionLocal therapeutic hypothermia (32°C) 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.Material and MethodsThe cochleae of C57Bl6/J mice (Charles River®, Freiburg, Germany) are cultured for 24 hours at 37°C and 32°C after inserting a fishing line through the round window simulating an insertion trauma. The resulting effect was evaluated for the apoptotic reaction – B-cell-Lymphoma-2-Associated-X-Protein (BAX), B-Cell-Lymphoma-2-Protein (BCL2) and Cleaved-Caspase-3 (CC3) –, the inflammatory response – Tumor-Necrosis-Factor-Alpha (TNFα), Interleukin-1-Beta (IL-1Imm) and Cyclooxygenase-2 (COX2) – and proliferation process – Transforming-Growth-Factor-Beta-1 (TGFβ1) – using immunohistochemistry and real-time PCR technique. A minimum of 12 cochlea per experiment were used.ResultsA pro-apoptotic situation was observed in the normothermic group (BAX, CC3 ˃ Bcl2) whereas an anti-apoptotic constellation was found at 32°C culture conditions (BAX, CC3 < Bcl2). Furthermore the effect of the IT knowing to effect the pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression has been reproduced. This reaction was reversed with the application of therapeutic hypothermia resulting in significant lower pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression. TGFβ1 was increased by hypothermia.DiscussionConcluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.

【 授权许可】

Unknown   
Copyright © 2023 Schmutzhard, Bader, Gottfried, Dejaco, Glückert, Dudas and Schrott-Fischer.