Conservation of Hearing and Protection of Auditory Hair Cells against Trauma-Induced Losses by Local Dexamethasone Therapy: Molecular and Genetic Mechanisms

Abstract

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.

Keywords:

• COCHLEAR IMPLANT
• DEXAMETHASONE
• TRAUMA
• HEARING LOSS
• CONSERVATION OF HEARING