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, Scott M. Haake, Gia Hoosien, Richard Vivero, Sherry Chan, Jao He, Adrien A. Eshraghi, Simon I. Angeli, Fred F. Telischi, Thomas J. Balkany

Research output: Contribution to journalArticle

27 Scopus citations

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 (US)
Pages (from-to)42-55
Number of pages14
JournalCochlear implants international
Volume11 Suppl 1
DOIs
StatePublished - Jun 2010

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Speech and Hearing

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