Abstract
ObjectiveTo investigate the effect of timing of dexamethasone administration on auditory hair cell survival following an ototoxic insult with kanamycin and furosemide.Study designControlled experimental study.SettingTranslational science experimental laboratory.Methods5–6 week old CBA/CaJ mice, divided into 6 groups, were injected with kanamycin (1 mg/g SC) followed by furosemide (0.5 mg/g IP). Dexamethasone (0.1 mg/g IP) was injected at either 1 hour prior to insult, +1 hr, +6 hr, +12 hr, or +72 hr post insult. Temporal bones harvested on day 7 underwent Organ of Corti dissection. Immunohistochemical staining was performed using antibodies to myosin 7a, phalloidin, and TO-PRO.ResultsHair cell counts demonstrate a uniform ototoxicity model with total loss of outer hair cells (OHCs) and near-total loss of inner hair cells (IHCs). The group pre-treated with dexamethasone showed a statistically significant improvement in counts compared to controls (p = 0.004). Counts from the other experimental groups given dexamethasone after the insult were highly variable but demonstrated some apical and middle turn inner hair cell survival.ConclusionTreatment of systemic dexamethasone prior to ototoxic insult attenuates hair cell loss in a reliable, novel, ototoxicity model using kanamycin and furosemide in CBA/CaJ mice. Dosing with dexamethasone following ototoxic insult shows promising yet variable response in hair cell survival.
Highlights
Administration of corticosteroids has been shown to attenuate the ototoxic effects of aminoglycoside in animal models [1,2,3]
The group pre-treated with dexamethasone showed a statistically significant improvement in counts compared to controls (p = 0.004)
After the ototoxic insult is given, is there a ‘golden hour’ of time in which corticosteroid administration will either prevent or minimize hair cell loss? The purpose of our study is to determine whether the benefits of corticosteroid protection can be extended to after the ototoxic drug is given by studying this effect in a novel adult mouse model of ototoxicity
Summary
Administration of corticosteroids has been shown to attenuate the ototoxic effects of aminoglycoside in animal models [1,2,3]. One of the difficulties for the treating physician is that corticosteroid dosing regiments are still quite variable and traditionally in the role of otoprotection, they are given prior to the initiation of treatment. It is not known if there is any role for administrating systemic corticosteroids after the ototoxic drug has been given. After the ototoxic insult is given, is there a ‘golden hour’ of time in which corticosteroid administration will either prevent or minimize hair cell loss? After the ototoxic insult is given, is there a ‘golden hour’ of time in which corticosteroid administration will either prevent or minimize hair cell loss? The purpose of our study is to determine whether the benefits of corticosteroid protection can be extended to after the ototoxic drug is given by studying this effect in a novel adult mouse model of ototoxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Otolaryngology - Head & Neck Surgery
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
