Mechanisms of hearing loss from trauma and inflammation: Otoprotective therapies from the laboratory to the clinic

This article reviews a series of in vitro and in vivo studies that examined the otoprotective efficacy of locally delivered dexamethasone and explored the mechanisms by which dexamethasone protects auditory hair cells. These studies used auditory threshold testing in response to pure tone stimuli, organ of Corti explant cultures, FITC-phalloidin-stained explants, and surface preparations to determine hair cell density, osmotic pump delivery of dexamethasone into the scala tympani, an animal model of electrode insertion trauma (EIT)-induced hearing loss, and real-time RT-PCR studies of gene expression levels. Local delivery of two different formulations of dexamethasone conserved hearing and protected hair cells in an animal model of cochlear implantation. Dexamethasone treatment protected hair cells in organ of Corti explants exposed to an ototoxic level of an inflammatory cytokine, and gene expression studies showed that this protection was accomplished by increased expression levels of anti-apoptosis genes (e.g. Bcl-2) and decreased levels of pro-apoptosis genes (e.g. Bax). We conclude that dexamethasone is an effective otoprotective drug for both the conservation of hearing and preservation of hair cells against trauma-induced losses. Locally delivered dexamethasone is a promising therapeutic approach for the conservation of hearing during the process of cochlear implantation.