Surviving murine experimental sepsis affects the function and morphology of the inner ear

Severe sepsis is known to result in various neurological long-term deficits in human. Recently, a link between severe, lethal sepsis and significant hearing loss with correlating histomorphological inner ear changes in mice (C57BL/6) was observed. However, if similar observations can be made in seve...

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Main Authors: Natalie Fischer, Nina Maria Mathonia, Georges Hoellerich, Julian Veser, Leyla Pinggera, Daniel Dejaco, Rudolf Glueckert, Anneliese Schrott-Fischer, Peter Lackner, Herbert Riechelmann, Joachim Schmutzhard
Format: Article
Language:English
Published: The Company of Biologists 2017-06-01
Series:Biology Open
Subjects:
Online Access:http://bio.biologists.org/content/6/6/732
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author Natalie Fischer
Nina Maria Mathonia
Georges Hoellerich
Julian Veser
Leyla Pinggera
Daniel Dejaco
Rudolf Glueckert
Anneliese Schrott-Fischer
Peter Lackner
Herbert Riechelmann
Joachim Schmutzhard
author_facet Natalie Fischer
Nina Maria Mathonia
Georges Hoellerich
Julian Veser
Leyla Pinggera
Daniel Dejaco
Rudolf Glueckert
Anneliese Schrott-Fischer
Peter Lackner
Herbert Riechelmann
Joachim Schmutzhard
author_sort Natalie Fischer
collection DOAJ
description Severe sepsis is known to result in various neurological long-term deficits in human. Recently, a link between severe, lethal sepsis and significant hearing loss with correlating histomorphological inner ear changes in mice (C57BL/6) was observed. However, if similar observations can be made in severe, non-lethal sepsis in mice is unclear. This study evaluates mice after severe, non-lethal sepsis for analogue functional and histomorphological alterations of the inner ear. A total of 63 C57BL/6 mice were included in the study. All underwent an initial hearing test with auditory brainstem response on day 1. In 35 mice sepsis was induced by cecal ligation and puncture (CLP), in 15 sham surgery was performed and 13 served as healthy control. A second hearing test was performed on day 7. All mice were sacrificed afterwards for further histomorphological evaluation of the inner ears. Immunohistochemical analysis with apoptotic markers Cleaved-caspase 3, BAX and BCL-2 were performed to identify structural inner ear damage. Of all CLP mice, 21/35 (60.0%) died due to the induced sepsis. Of the surviving CLP mice, 14/35 (40.0%), post-treatment hearing thresholds differed significantly from the sham and control mice (P<0.001). Positive immunostaining at different inner ear structures, like the spiral ligament or the supporting cells could be observed. The percentage of the immunostained positive area in the spiral ligament significantly correlated with the grade of hearing loss for BAX (P=0.027) and Cleaved-caspase 3 (P=0.024) but not for BCL 2 (P>0.05). The present data suggests that severe, non-lethal sepsis in mice results in significantly elevated hearing thresholds. A positive labelling for the pro-apoptotic markers BAX and Cleaved-caspase 3 suggested the induction of apoptosis in inner ear.
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spelling doaj.art-b7a0eae917e74ca5ac51689b5f08c8d02022-12-21T22:52:22ZengThe Company of BiologistsBiology Open2046-63902017-06-016673274010.1242/bio.024588024588Surviving murine experimental sepsis affects the function and morphology of the inner earNatalie Fischer0Nina Maria Mathonia1Georges Hoellerich2Julian Veser3Leyla Pinggera4Daniel Dejaco5Rudolf Glueckert6Anneliese Schrott-Fischer7Peter Lackner8Herbert Riechelmann9Joachim Schmutzhard10 Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Department of Otorhinolaryngology, Medical University of Innsbruck, 6020 Innsbruck, Austria Severe sepsis is known to result in various neurological long-term deficits in human. Recently, a link between severe, lethal sepsis and significant hearing loss with correlating histomorphological inner ear changes in mice (C57BL/6) was observed. However, if similar observations can be made in severe, non-lethal sepsis in mice is unclear. This study evaluates mice after severe, non-lethal sepsis for analogue functional and histomorphological alterations of the inner ear. A total of 63 C57BL/6 mice were included in the study. All underwent an initial hearing test with auditory brainstem response on day 1. In 35 mice sepsis was induced by cecal ligation and puncture (CLP), in 15 sham surgery was performed and 13 served as healthy control. A second hearing test was performed on day 7. All mice were sacrificed afterwards for further histomorphological evaluation of the inner ears. Immunohistochemical analysis with apoptotic markers Cleaved-caspase 3, BAX and BCL-2 were performed to identify structural inner ear damage. Of all CLP mice, 21/35 (60.0%) died due to the induced sepsis. Of the surviving CLP mice, 14/35 (40.0%), post-treatment hearing thresholds differed significantly from the sham and control mice (P<0.001). Positive immunostaining at different inner ear structures, like the spiral ligament or the supporting cells could be observed. The percentage of the immunostained positive area in the spiral ligament significantly correlated with the grade of hearing loss for BAX (P=0.027) and Cleaved-caspase 3 (P=0.024) but not for BCL 2 (P>0.05). The present data suggests that severe, non-lethal sepsis in mice results in significantly elevated hearing thresholds. A positive labelling for the pro-apoptotic markers BAX and Cleaved-caspase 3 suggested the induction of apoptosis in inner ear.http://bio.biologists.org/content/6/6/732SepsisHearing lossInner earInflammationApoptosis
spellingShingle Natalie Fischer
Nina Maria Mathonia
Georges Hoellerich
Julian Veser
Leyla Pinggera
Daniel Dejaco
Rudolf Glueckert
Anneliese Schrott-Fischer
Peter Lackner
Herbert Riechelmann
Joachim Schmutzhard
Surviving murine experimental sepsis affects the function and morphology of the inner ear
Biology Open
Sepsis
Hearing loss
Inner ear
Inflammation
Apoptosis
title Surviving murine experimental sepsis affects the function and morphology of the inner ear
title_full Surviving murine experimental sepsis affects the function and morphology of the inner ear
title_fullStr Surviving murine experimental sepsis affects the function and morphology of the inner ear
title_full_unstemmed Surviving murine experimental sepsis affects the function and morphology of the inner ear
title_short Surviving murine experimental sepsis affects the function and morphology of the inner ear
title_sort surviving murine experimental sepsis affects the function and morphology of the inner ear
topic Sepsis
Hearing loss
Inner ear
Inflammation
Apoptosis
url http://bio.biologists.org/content/6/6/732
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