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

Published

Journal Article

HYPOTHESIS: Dexamethasone (DXM) protects hearing against trauma-induced loss. MATERIALS: 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. RESULTS: 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). CONCLUSIONS: DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.

Full Text

Duke Authors

Cited Authors

  • Van De Water, TR; Abi Hachem, RN; Dinh, CT; Bas, E; Haake, SM; Hoosien, G; Vivero, R; Chan, S; He, J; Eshraghi, AA; Angeli, SI; Telischi, FF; Balkany, TJ

Published Date

  • June 2010

Published In

Volume / Issue

  • 11 Suppl 1 /

Start / End Page

  • 42 - 55

PubMed ID

  • 21756583

Pubmed Central ID

  • 21756583

Electronic International Standard Serial Number (EISSN)

  • 1754-7628

International Standard Serial Number (ISSN)

  • 1467-0100

Digital Object Identifier (DOI)

  • 10.1179/146701010x12671178390834

Language

  • eng