A novel combination of drug therapy to protect residual hearing post cochlear implant surgery

Adrien Eshraghi, Jonathan Roell, Noah Shaikh, Fred F Telischi, Blake Bauer, Mateo Guardiola, Esperanza Bas Infante, Thomas R Van De Water, Ileana Rivera, Jeenu Mittal

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. Control group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cells in vitro. Their combination provided close to 96% protection, demonstrating an additive effect.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalActa Oto-Laryngologica
DOIs
StateAccepted/In press - Feb 3 2016

Fingerprint

Cochlear Implants
Combination Drug Therapy
Hearing
Mannitol
Electrodes
Acetylcysteine
Wounds and Injuries
Cochlea
Alopecia
Cytoprotection
Inner Ear
Hearing Loss
Control Groups
Dexamethasone
Cell Death
Multiple Trauma
Serum-Free Culture Media
Cell Count

Keywords

  • apoptosis
  • cochlear implantation
  • hair cell loss
  • Inner ear trauma
  • otoprotection

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

A novel combination of drug therapy to protect residual hearing post cochlear implant surgery. / Eshraghi, Adrien; Roell, Jonathan; Shaikh, Noah; Telischi, Fred F; Bauer, Blake; Guardiola, Mateo; Bas Infante, Esperanza; Van De Water, Thomas R; Rivera, Ileana; Mittal, Jeenu.

In: Acta Oto-Laryngologica, 03.02.2016, p. 1-5.

Research output: Contribution to journalArticle

Eshraghi, Adrien ; Roell, Jonathan ; Shaikh, Noah ; Telischi, Fred F ; Bauer, Blake ; Guardiola, Mateo ; Bas Infante, Esperanza ; Van De Water, Thomas R ; Rivera, Ileana ; Mittal, Jeenu. / A novel combination of drug therapy to protect residual hearing post cochlear implant surgery. In: Acta Oto-Laryngologica. 2016 ; pp. 1-5.
@article{8eb928baf5144ad6a8997572ce073a1a,
title = "A novel combination of drug therapy to protect residual hearing post cochlear implant surgery",
abstract = "Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. Control group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50{\%} protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50{\%} protection of hair cells in vitro. Their combination provided close to 96{\%} protection, demonstrating an additive effect.",
keywords = "apoptosis, cochlear implantation, hair cell loss, Inner ear trauma, otoprotection",
author = "Adrien Eshraghi and Jonathan Roell and Noah Shaikh and Telischi, {Fred F} and Blake Bauer and Mateo Guardiola and {Bas Infante}, Esperanza and {Van De Water}, {Thomas R} and Ileana Rivera and Jeenu Mittal",
year = "2016",
month = "2",
day = "3",
doi = "10.3109/00016489.2015.1134809",
language = "English (US)",
pages = "1--5",
journal = "Acta Oto-Laryngologica",
issn = "0001-6489",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - A novel combination of drug therapy to protect residual hearing post cochlear implant surgery

AU - Eshraghi, Adrien

AU - Roell, Jonathan

AU - Shaikh, Noah

AU - Telischi, Fred F

AU - Bauer, Blake

AU - Guardiola, Mateo

AU - Bas Infante, Esperanza

AU - Van De Water, Thomas R

AU - Rivera, Ileana

AU - Mittal, Jeenu

PY - 2016/2/3

Y1 - 2016/2/3

N2 - Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. Control group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cells in vitro. Their combination provided close to 96% protection, demonstrating an additive effect.

AB - Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. Control group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cells in vitro. Their combination provided close to 96% protection, demonstrating an additive effect.

KW - apoptosis

KW - cochlear implantation

KW - hair cell loss

KW - Inner ear trauma

KW - otoprotection

UR - http://www.scopus.com/inward/record.url?scp=84958522571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958522571&partnerID=8YFLogxK

U2 - 10.3109/00016489.2015.1134809

DO - 10.3109/00016489.2015.1134809

M3 - Article

C2 - 26854005

AN - SCOPUS:84958522571

SP - 1

EP - 5

JO - Acta Oto-Laryngologica

JF - Acta Oto-Laryngologica

SN - 0001-6489

ER -