Conservation of hearing and protection of auditory hair cells against trauma-induced losses by local dexamethasone therapy: molecular and genetic mechanisms.
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.
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Related Subject Headings
- Wounds and Injuries
- Up-Regulation
- Tumor Necrosis Factor-alpha
- Reference Values
- Real-Time Polymerase Chain Reaction
- Random Allocation
- Otorhinolaryngology
- Organ of Corti
- In Vitro Techniques
- Hearing Loss
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Wounds and Injuries
- Up-Regulation
- Tumor Necrosis Factor-alpha
- Reference Values
- Real-Time Polymerase Chain Reaction
- Random Allocation
- Otorhinolaryngology
- Organ of Corti
- In Vitro Techniques
- Hearing Loss