HYPOTHESIS: How to induce most efficiently severe sensorineural hearing loss in mice using a single coadministration of an aminoglycoside antibiotic and a loop diuretic? BACKGROUND: The coadministration of aminoglycosides and a loop diuretic has been widely used to induce hair cell and spiral ganglion cell loss in guinea pigs. However, the development of new treatment strategies against sensorineural hearing loss, such as tissue engineering techniques, requires the use of mouse models. Previous attempts to induce hearing loss in mice have rendered inconsistent results because of resistance to aminoglycoside-induced ototoxicity. Especially inner hair cells seem to be resistant to aminoglycoside-induced ototoxicity. METHODS: In the present study, we aim to optimize hearing loss in mice, using a single high-dose kanamycin (700 and 1,000 mg/kg) injection followed by a furosemide (100 mg/kg) administration. Although previous studies used intraperitoneal furosemide injections 30 minutes after kanamycin administration, we used intravenous furosemide injections administered within 5 minutes after kanamycin treatment. RESULTS: Auditory brain stem responses illustrated severe threshold shifts, and histologic analysis showed marked outer hair cell destruction as well as spiral ganglion cell loss. The present protocol results in more severe inner hair cell loss when compared with the results of previous researches. CONCLUSION: We conclude that severe sensorineural hearing loss can be induced in mice. Moreover, we found that this mouse model can be augmented via the use of rapid intravenous furosemide administrations to maximize inner hair cell loss.
HYPOTHESIS: How to induce most efficiently severe sensorineural hearing loss in mice using a single coadministration of an aminoglycoside antibiotic and a loop diuretic? BACKGROUND: The coadministration of aminoglycosides and a loop diuretic has been widely used to induce hair cell and spiral ganglion cell loss in guinea pigs. However, the development of new treatment strategies against sensorineural hearing loss, such as tissue engineering techniques, requires the use of mouse models. Previous attempts to induce hearing loss in mice have rendered inconsistent results because of resistance to aminoglycoside-induced ototoxicity. Especially inner hair cells seem to be resistant to aminoglycoside-induced ototoxicity. METHODS: In the present study, we aim to optimize hearing loss in mice, using a single high-dose kanamycin (700 and 1,000 mg/kg) injection followed by a furosemide (100 mg/kg) administration. Although previous studies used intraperitoneal furosemide injections 30 minutes after kanamycin administration, we used intravenous furosemide injections administered within 5 minutes after kanamycin treatment. RESULTS: Auditory brain stem responses illustrated severe threshold shifts, and histologic analysis showed marked outer hair cell destruction as well as spiral ganglion cell loss. The present protocol results in more severe inner hair cell loss when compared with the results of previous researches. CONCLUSION: We conclude that severe sensorineural hearing loss can be induced in mice. Moreover, we found that this mouse model can be augmented via the use of rapid intravenous furosemide administrations to maximize inner hair cell loss.