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

INTRODUCTION: Local 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 mechan...

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Autores principales: Schmutzhard, Joachim, Bader, Werner, Gottfried, Timo, Dejaco, Daniel, Glückert, Rudolf, Dudas, Joszef, Schrott-Fischer, Annelies
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10133490/
https://www.ncbi.nlm.nih.gov/pubmed/37123355
http://dx.doi.org/10.3389/fnins.2023.1112243
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author Schmutzhard, Joachim
Bader, Werner
Gottfried, Timo
Dejaco, Daniel
Glückert, Rudolf
Dudas, Joszef
Schrott-Fischer, Annelies
author_facet Schmutzhard, Joachim
Bader, Werner
Gottfried, Timo
Dejaco, Daniel
Glückert, Rudolf
Dudas, Joszef
Schrott-Fischer, Annelies
author_sort Schmutzhard, Joachim
collection PubMed
description INTRODUCTION: Local 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 METHODS: The 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. RESULTS: A 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. DISCUSSION: Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.
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spelling pubmed-101334902023-04-28 The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture Schmutzhard, Joachim Bader, Werner Gottfried, Timo Dejaco, Daniel Glückert, Rudolf Dudas, Joszef Schrott-Fischer, Annelies Front Neurosci Neuroscience INTRODUCTION: Local 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 METHODS: The 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. RESULTS: A 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. DISCUSSION: Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction. Frontiers Media S.A. 2023-04-13 /pmc/articles/PMC10133490/ /pubmed/37123355 http://dx.doi.org/10.3389/fnins.2023.1112243 Text en Copyright © 2023 Schmutzhard, Bader, Gottfried, Dejaco, Glückert, Dudas and Schrott-Fischer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Schmutzhard, Joachim
Bader, Werner
Gottfried, Timo
Dejaco, Daniel
Glückert, Rudolf
Dudas, Joszef
Schrott-Fischer, Annelies
The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title_full The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title_fullStr The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title_full_unstemmed The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title_short The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
title_sort effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10133490/
https://www.ncbi.nlm.nih.gov/pubmed/37123355
http://dx.doi.org/10.3389/fnins.2023.1112243
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