Biopolymer-released dexamethasone prevents tumor necrosis factor alpha-induced loss of auditory hair cells in vitro: implications toward the development of a drug-eluting cochlear implant electrode array.

Dinh C, Hoang K, Haake S, Chen S, Angeli S, Nong E, Eshraghi AA, Balkany TJ, Van De Water TR
Otol Neurotol. 2008 29 (7): 1012-9

PMID: 18818545 · DOI:10.1097/MAO.0b013e3181859a1f

HYPOTHESIS - Polymer-eluted dexamethasone (DXM) will retain its ability to protect against tumor necrosis factor alpha (TNFalpha)-induced hair cell (HC) loss.

BACKGROUND - TNFalpha has been shown to be associated with trauma-induced hearing loss. DXM has been demonstrated to protect the cochlea against trauma-induced hearing loss. DXM is currently administered either systemically or locally to treat patients with sudden hearing loss of unknown cause.

METHODS - P-3 organ of Corti explants challenged with an ototoxic level of TNFalpha was the experimental system, and the base form of DXM (DXMb) incorporated into a biorelease polymer (i.e., SIBS) was the otoprotection molecule tested. The efficacy of otoprotection was determined by counts of fluorescein isothiocyanate-phalloidin-stained HCs and changes in gene expression.

RESULTS - HC counts show 1) SIBS alone did not protect HCs from TNFalpha ototoxicity (SIBS versus SIBS + TNFalpha; p < 0.001), and 2) SIBS with DXMb provides a significant level of protection against TNFalpha-induced loss of HCs (TNFalpha + SIBS versus TNFalpha + SIBS/DXMb, 299 mug; p < 0.001). Gene expression results show that polymer-eluted DXMb 1) upregulates antiapoptotic genes (i.e., Bcl-2, Bcl-xl) and downregulates a proapoptotic gene (i.e., Bax) in TNFalpha-challenged explants and 2) downregulates TNFR1 in these explants.

CONCLUSION - Polymer-eluted DXMb retains its otoprotection capabilities in our in vitro test system of TNFalpha-challenged organ of Corti explants by altering the pattern of gene expression to favor survival of TNFalpha-exposed HCs. These results, although in vitro, support the application of polymer containing DXMb to electrode arrays for the conservation of hearing during cochlear implantation.

MeSH Terms (13)

Animals Animals, Newborn Biopolymers Cochlear Implants Delayed-Action Preparations Dexamethasone Hair Cells, Auditory Hearing Loss Organ of Corti Prosthesis Design Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha

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