Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result of lack of animal models of N-ethyl-N-nitrosourea(ENU) induced mutations in otitis media with effusion(OME).Methods Otoscopy and auditory brain response(ABR) evaluation were carried out under sedation in Nmf391nmf/nmf mice of 2,4,6 and 8 months of age.The mice were killed for study of middle and inner ear pathology.Results Tympanic membrane visualization and ABR thresholds in 1-to 8-month-old Nmf391nmf/nmf mice showed spontaneous OME and inner ear diseases in approximately 100% of the animals.The significant elevation of ABR thresholds suggested a sensorineural component in hearing loss in addition to the conductive loss.Middle and inner ear histology showed various degrees of outer hair cells loss and middle ear inflammation in all the mice,but no inflammation cells in the inner ear.The ABR threshold at 32 kHz was significantly elevated.Conclusions This study shows histopathologic changes in the Nmf391nmf/nmf mouse model of COM with effusion that have not been reported in human COM.This ENU induced mutation model of COM will be valuable for the characterization of middle ear inflammation and inner ear disease processes that are induced by middle ear infections.We propose that COM with effusion in this ENU induced mutation model is the cause of the cochlea hair cells damage.
Objective To study the recovery of the outer hair cells in the bat cochlea after gentamicin exposure. Methods Bats were injected with a daily dose of gentamicin for 15 consecutive days and bromodeoxyuridine (BrdU) was given from day 16 to day 40 of this recovery phase. Hearing was assessed by overt acoustic behavior and auditory brainstem responses analysis, which was performed one day prior to the first injection and a day after the last injection (day 16). On day 40 animals were sacrificed for detection of cells that could take up BrdU. Results After 15 days of gentamicin treatment, all of the animals were proved to be deafened with significant increases of ABR thresholds, compared with control group. The findings in immunocytochemical stained samples and scanning electron microscopy revealed that BrdU labeled nuclei were observed in the cochlea in all of the deafened animals most commonly in the regions of the first-row and second-row Deiter’s cells (DCs) and occasionally in the regions of the third-row DCs. Conclusion We suggest that, under sufficient drug and enough time, the bat cochlear supporting cells can directly transdifferentiate into the outer hair cells after aminoglycoside exposure. This transdifferentation process is essential for repair of outer hair cells and recovery of normal function after gentamicin exposure.
