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Deafness induction in mice.

Thijs T G Jansen1, Hendrik G Bremer, Vedat Topsakal

  • 1Department of Otorhinolaryngology and Head & Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [And] European Academy of Otology and Neurotology
|July 26, 2013
PubMed
Summary
This summary is machine-generated.

This study optimized a method to induce severe sensorineural hearing loss in mice using kanamycin and furosemide. Rapid intravenous furosemide administration maximized hair cell damage, creating a valuable model for hearing loss research.

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Area of Science:

  • Ototoxicity research
  • Auditory neuroscience
  • Animal models for hearing loss

Background:

  • Aminoglycosides and loop diuretics induce hearing loss in guinea pigs.
  • Mouse models are crucial for developing new sensorineural hearing loss treatments.
  • Previous mouse models showed inconsistent results due to aminoglycoside resistance, particularly in inner hair cells.

Purpose of the Study:

  • To establish an efficient method for inducing severe sensorineural hearing loss in mice.
  • To optimize the coadministration of an aminoglycoside antibiotic and a loop diuretic for ototoxicity.
  • To overcome resistance to aminoglycoside-induced ototoxicity in mouse inner hair cells.

Main Methods:

  • Administered high-dose kanamycin (700-1,000 mg/kg) followed by furosemide (100 mg/kg) in mice.
  • Utilized rapid intravenous furosemide injections within 5 minutes post-kanamycin.
  • Compared this protocol to previous methods using intraperitoneal furosemide 30 minutes after kanamycin.

Main Results:

  • Auditory brain stem responses revealed significant threshold shifts, indicating hearing loss.
  • Histologic analysis confirmed substantial outer hair cell destruction and spiral ganglion cell loss.
  • The optimized protocol resulted in more severe inner hair cell loss than previously reported.

Conclusions:

  • Severe sensorineural hearing loss can be reliably induced in mice.
  • Rapid intravenous furosemide administration enhances ototoxicity, maximizing inner hair cell loss.
  • This refined mouse model is suitable for investigating novel sensorineural hearing loss therapies.