Development of an ototoxicity model in the adult CBA/CaJ mouse and determination of a golden window of corticosteroid intervention for otoprotection.
OBJECTIVE
To investigate the effect of timing of dexamethasone administration on auditory hair cell survival following an ototoxic insult with kanamycin and furosemide.


METHODS
Controlled experimental study.


METHODS
Translational science experimental laboratory.


METHODS
5-6 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.


RESULTS
Hair 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.


CONCLUSIONS
Treatment 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.
Vinay T
VT
Fernandes
Department of Otolaryngolgy - Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Suite M1-102, Toronto, ON M4N 3M5, Canada. Vincent.Lin@sunnybrook.ca.
Vincent Y W
VY
Lin
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005665:Furosemide / Q000633:toxicity*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D007612:Kanamycin / Q000633:toxicity*; D008297:Male; D008808:Mice, Inbred CBA; D011292:Premedication; D013997:Time Factors; D057170:Translational Research, Biomedical
D007612:Kanamycin; D005665:Furosemide; D003907:Dexamethasone