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Polymer‐eluted Dexamethasone Protects Hearing and Hair Cells Against Trauma‐induced Loss
Author(s) -
Van De Water Thomas R,
Hachem Ralph Abi,
Bohorquez Jorge,
Eshraghi Adrien A,
Angeli Simon,
Balkany Thomas J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb29
Subject(s) - downregulation and upregulation , apoptosis , tumor necrosis factor alpha , dexamethasone , inflammation , microbiology and biotechnology , gene expression , in vitro , chemistry , gene , biology , immunology , endocrinology , biochemistry
Objective Investigate the efficacy of polymer‐eluted dexamethasone base (DXMb) to protect hearing & auditory hair cells against trauma‐induced losses. Methods An animal model of EIT‐induced loss of auditory function/hair cells and an in vitro model of inflammatory cytokine‐induced apoptosis of hair cells tested the otoprotective efficacy of polymer (SIBS)‐eluted DXMb. Inhibitor and gene expression studies quantified the expression levels of selected apoptosis and inflammation‐related genes. Results DXMb‐eluted from SIBS‐coated electrodes conserved hearing & protected hair cells in an animal model of cochlear implantation. Inhibitor studies demonstrated that NFκB is required for otoprotection. Bax, Bcl‐2, Bcl‐xl & TNFR1 genes were identified as targets of NFκB within TNFα‐challenged/DXMb‐treated explants. TNFα upregulated Bax & TNFR1 and downregulated Bcl‐2 & Bcl‐xl , treatment of these explants with eluted‐DXMb reversed TNFα‐induced changes by downregulation of Bax & TNFR1 and upregulation Bcl‐2 & Bcl‐xl . DXMb‐treatment also reversed TNFα‐induced elevation of the inflammation related gene, TNFR1 . Conclusions Polymer‐eluted DXMb retains its otoprotective efficacy activating NFκB signaling which, upregulates anti‐apoptosis related genes, and downregulates pro‐apoptosis & pro‐inflammatory genes. Supported by a grant from the MED‐EL Corp., Innsbruck, Austria