Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis

A dose response study

Esperanza Bas Infante, Jorge Bohorquez, Stefania Goncalves, Enrique Perez, Christine T Dinh, Carolyn Garnham, Roland Hessler, Adrien Eshraghi, Thomas R Van De Water

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27 Citations (Scopus)

Abstract

We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.

Original languageEnglish (US)
Pages (from-to)12-24
Number of pages13
JournalHearing Research
Volume337
DOIs
StatePublished - Jul 1 2016

Fingerprint

Alopecia
Electric Impedance
Dexamethasone
Hearing
Electrodes
Fibrosis
Wounds and Injuries
Cochlea
Organ of Corti
Hearing Loss
Guinea Pigs
Scala Tympani
Cochlear Implantation
Silicones

Keywords

  • Cochlear implantation
  • Hair cell loss
  • Hearing loss
  • Increased impedance
  • Insertion trauma
  • Local delivery of dexamethasone
  • Otoprotection

ASJC Scopus subject areas

  • Sensory Systems

Cite this

@article{a6e5d48fc54247d0b58fbd70770d5143,
title = "Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study",
abstract = "We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10{\%}, 1{\%}, 0.1{\%}, or 0{\%} levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10{\%} or 1.0{\%} DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1{\%} DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.",
keywords = "Cochlear implantation, Hair cell loss, Hearing loss, Increased impedance, Insertion trauma, Local delivery of dexamethasone, Otoprotection",
author = "{Bas Infante}, Esperanza and Jorge Bohorquez and Stefania Goncalves and Enrique Perez and Dinh, {Christine T} and Carolyn Garnham and Roland Hessler and Adrien Eshraghi and {Van De Water}, {Thomas R}",
year = "2016",
month = "7",
day = "1",
doi = "10.1016/j.heares.2016.02.003",
language = "English (US)",
volume = "337",
pages = "12--24",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",

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TY - JOUR

T1 - Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis

T2 - A dose response study

AU - Bas Infante, Esperanza

AU - Bohorquez, Jorge

AU - Goncalves, Stefania

AU - Perez, Enrique

AU - Dinh, Christine T

AU - Garnham, Carolyn

AU - Hessler, Roland

AU - Eshraghi, Adrien

AU - Van De Water, Thomas R

PY - 2016/7/1

Y1 - 2016/7/1

N2 - We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.

AB - We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.

KW - Cochlear implantation

KW - Hair cell loss

KW - Hearing loss

KW - Increased impedance

KW - Insertion trauma

KW - Local delivery of dexamethasone

KW - Otoprotection

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U2 - 10.1016/j.heares.2016.02.003

DO - 10.1016/j.heares.2016.02.003

M3 - Article

VL - 337

SP - 12

EP - 24

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

ER -