Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling
Objectives/Hypothesis: To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111. Study Design: An animal model of cochlear implantation. Methods: Guinea pigs' hearing thresholds were measured by auditor...
Saved in:
| Published in: | The Laryngoscope Vol. 123; no. S1; pp. S1 - S14 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01-03-2013
Wiley Subscription Services, Inc |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Objectives/Hypothesis:
To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111.
Study Design:
An animal model of cochlear implantation.
Methods:
Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM‐111 30 minutes before EIT (EIT+AM‐111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)‐phalloidin staining for hair cell counts were performed at 90 days post‐EIT. Immunostaining for 4‐hydroxy‐2‐nonenal (HNE), activated caspase‐3, CellROX, and phospho‐c‐Jun were performed at 24 hours post‐EIT.
Results:
ABR thresholds increased post‐EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM‐111 treated or unoperated control ears. AM‐111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post‐EIT. Immunostaining of 24‐hour post‐EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase‐3 was observed only in SCs, and phosphorylation of c‐Jun occurred only in HCs of the EIT‐only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase‐3, or phospho‐c‐Jun in the organ of Corti specimens from AM‐111 treated cochleae.
Conclusions:
Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM‐111 provided a significant level of protection against EIT‐induced hearing losses, HC losses, and damage to neural elements. Laryngoscope, 123:S1–S14, 2013 |
|---|---|
| Bibliography: | The authors have no other funding, financial relationships, or conflicts of interest to disclose. This work was performed at the University of Miami Hearing Research Laboratory, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida. ark:/67375/WNG-PMHVLMFF-5 istex:4E711D15E2A08046D4775E02DE94438B2CF5AB5F ArticleID:LARY23902 This article is a Triological Society thesis for Dr. Adrien A. Eshraghi. It was selected by the Triological Society Council to receive "Honorable Mention Award in Basic Science Research Competition" and will be presented at the Combined Sections Meeting, January 24-26, 2013. This study was funded by research grants to Dr. Adrien Eshraghi from MED-EL GmbH, Innsbruck, Austria, and the National Organization for Hearing Research (NOHR). Dr. Eshraghi has received financial compensation as a consultant for MED-EL GmbH. The authors have no financial relationship with Auris Medical. This article is a Triological Society thesis for Dr. Adrien A. Eshraghi. It was selected by the Triological Society Council to receive “Honorable Mention Award in Basic Science Research Competition” and will be presented at the Combined Sections Meeting, January 24–26, 2013. This study was funded by research grants to Dr. Adrien Eshraghi from MED‐EL GmbH, Innsbruck, Austria, and the National Organization for Hearing Research (NOHR). Dr. Eshraghi has received financial compensation as a consultant for MED‐EL GmbH. The authors have no financial relationship with Auris Medical. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0023-852X 1531-4995 |
| DOI: | 10.1002/lary.23902 |