Conservation of hearing and protection of auditory hair cells against trauma-induced losses by local dexamethasone therapy: molecular and genetic mechanisms.

Thomas R Van De Water, Ralph N. Abi Hachem, Christine T Dinh, Esperanza Bas Infante, Scott M. Haake, Gia Hoosien, Richard Vivero, Sherry Chan, Jao He, Adrien Eshraghi, Simon I Angeli, Fred F Telischi, Thomas J. Balkany

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Dexamethasone (DXM) protects hearing against trauma-induced loss. in vivo: A guinea pig model of electrode induced trauma (EIT)-induced hearing loss was used to locally deliver dexamethasone. In vitro: TNF-α-challenged organ of Corti explants treated with DXM or polymer-eluted DXM +/- PI3K/Akt/PkB/NFkB inhibitors were used for hair cells count and gene expression studies. in vivo: local DXM treatment of EIT-animals prevents trauma-induced loss of ABR thresholds that occurs in EIT-animals and EIT-animals treated with the carrier solution (i.e., AP), and prevented loss of auditory hair cells. In vitro: DXM and polymer-eluted DXM were equally effective in protecting hair cells from ototoxic levels of TNF-α Inhibitor treated explants demonstrated that DXM treatment requires both Akt/PKB and NFkB signalling for otoprotection. DXM treatment of explants showed up regulation of anti-apoptosis related genes (i.e., Bcl-2, Bcl-xl) and down regulation of pro-apoptosis related genes (i.e., Bax, TNFR-1). DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.

Original languageEnglish
Pages (from-to)42-55
Number of pages14
JournalCochlear Implants International
Volume11 Suppl 1
StatePublished - Jun 1 2010

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Auditory Hair Cells
Dexamethasone
Hearing
Molecular Biology
Wounds and Injuries
Electrodes
Apoptosis
Therapeutics
Polymers
bcl-2 Genes
Organ of Corti
Phosphatidylinositol 3-Kinases
Hearing Loss
Genes
Guinea Pigs
Up-Regulation

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Speech and Hearing

Cite this

Conservation of hearing and protection of auditory hair cells against trauma-induced losses by local dexamethasone therapy : molecular and genetic mechanisms. / Van De Water, Thomas R; Abi Hachem, Ralph N.; Dinh, Christine T; Bas Infante, Esperanza; Haake, Scott M.; Hoosien, Gia; Vivero, Richard; Chan, Sherry; He, Jao; Eshraghi, Adrien; Angeli, Simon I; Telischi, Fred F; Balkany, Thomas J.

In: Cochlear Implants International, Vol. 11 Suppl 1, 01.06.2010, p. 42-55.

Research output: Contribution to journalArticle

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