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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Role of mannitol in reducing postischemic changes in distortion-product otoacoustic emissions (DPOAEs): a rabbit
Krzysztof Morawski1, Fred F Telischi, Faisal Merchant
1Ear, Nose, and Throat Department, Silesian Medical Academy, Zabrze, Poland.
Objectives:
The aim of this study was to observe the effects of mannitol, administered topically at the round window (RW), on cochlear blood flow (CBF) and distortion-product otoacoustic emission (DPOAE) after repeated episodes of cochlear ischemia.
Methods:
Ten young rabbits were used for this study. Reversible ischemic episodes within the cochlea were induced by directly compressing the internal auditory artery (IAA). CBF was measured using a laser-Doppler (LD) probe positioned at the RW niche. DPOAEs were measured at 4, 8, and 12 kHz geometric mean frequency (GMF) using 60 dB sound pressure level (SPL) primary tone stimuli. In five test ears, mannitol was administered topically at the RW for 30 minutes before the IAA compressions. In five control ears, the IAA compressions were undertaken without application of RW medication. Each ear underwent three 5 minute IAA compressions with a 60 minute rest period between compressions.
Results:
In the control animals, it was observed that a progressive reduction in DPOAE level followed each successive IAA compression at all three test frequencies. The reduction in DPOAE amplitudes was consistently greater at the higher test frequencies. In the test rabbits, the RW administration of mannitol resulted in significantly less reduction in DPOAE level measures after repeated IAA compressions. For example, 30 minutes after reperfusion at 12 kHz GMF, DPOAE levels in the control ears were reduced by 1.5, 6.0, and 16 dB, compared with 1.5, 4.0, and 6.0 dB in the mannitol test ears.
Conclusions:
Mannitol appears to exert a protective effect on cochlear function after periods of ischemia. The RW appears to be an efficacious route for topical administration of mannitol into the inner ear.
Insights
Topical mannitol applied to the round window protected cochlear function from ischemic damage. This treatment reduced hearing loss from repeated cochlear ischemia episodes in rabbits.
Area of Science:
- Otoacoustic emissions and cochlear blood flow research.
- Inner ear physiology and pharmacology.
Background:
- Cochlear ischemia can lead to hearing loss.
- Protecting the cochlea from ischemia is crucial for preserving auditory function.
Purpose of the Study:
- To investigate the protective effects of topical mannitol on the cochlea.
- To assess mannitol's impact on cochlear blood flow (CBF) and distortion-product otoacoustic emissions (DPOAEs) following repeated ischemia.
Main Methods:
- Rabbits underwent repeated internal auditory artery (IAA) compressions to induce cochlear ischemia.
- Cochlear blood flow was measured using laser-Doppler at the round window (RW).
- Distortion-product otoacoustic emissions were recorded at 4, 8, and 12 kHz GMF. Mannitol was applied topically to the RW in test ears.
Main Results:
- Control ears showed progressive DPOAE reduction with successive ischemia episodes, especially at higher frequencies.
- Mannitol treatment significantly lessened DPOAE reduction after repeated ischemia.
- Example: At 12 kHz GMF, DPOAE reduction was 16 dB in control ears vs. 6 dB in mannitol-treated ears after reperfusion.
Conclusions:
- Topical mannitol applied to the round window demonstrates a protective effect on cochlear function against ischemia.
- The round window is an effective delivery route for mannitol into the inner ear.

