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Scott Haake
Last active: 3/3/2020

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

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
Cochlear Implants Int. 2010 11 Suppl 1: 42-55

PMID: 21756583 · DOI:10.1179/146701010X12671178390834

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.

MeSH Terms (21)

Animals Apoptosis Auditory Threshold Cells, Cultured Dexamethasone Disease Models, Animal Down-Regulation Electrodes, Implanted Gene Expression Regulation GTPase-Activating Proteins Guinea Pigs Hair Cells, Auditory Hearing Loss In Vitro Techniques Organ of Corti Random Allocation Real-Time Polymerase Chain Reaction Reference Values Tumor Necrosis Factor-alpha Up-Regulation Wounds and Injuries

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