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Updated: Apr 15, 2026

Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
Published on: February 10, 2023
Macrophage Migration Inhibitory Factor Deficiency Causes Prolonged Hearing Loss After Acoustic Overstimulation
Shin Kariya1, Mitsuhiro Okano, Yukihide Maeda
1*Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama; and †Department of Medical Bioinformatics, Hokkaido Information University, Hokkaido, Japan.
Hypothesis:
Macrophage migration inhibitory factor plays an important role in noise-induced hearing loss.
Background:
Macrophage migration inhibitory factor is an essential factor in axis formation and neural development. Macrophage migration inhibitory factor is expressed in the inner ear, but its function remains to be elucidated.
Methods:
Macrophage migration inhibitory factor-deficient mice (MIF(-/-) mice) were used in this study. Wild-type and MIF(-/-) mice received noise exposure composed of octave band noise. Auditory brainstem response thresholds were examined before (control) and at 0, 12, and 24 hours and 2 weeks after the intense noise exposure. Morphological findings of cochlear hair cells were investigated using scanning electron microscopy. Histopathological examination with hematoxylin and eosin staining and TUNEL assay were also performed.
Results:
In both the wild-type and MIF(-/-) mice, acoustic overstimulation induced significant hearing loss compared with the control level. Two weeks after the intense noise exposure, the MIF(-/-) mice had an increased hearing threshold compared with the wild-type mice. Scanning electron microscopy demonstrated that the outer hair cells in the MIF(-/-) mice were affected 2 weeks after noise exposure compared with the wild-type mice. TUNEL-positive cells were identified in the organ of Corti of the MIF(-/-) mice.
Conclusion:
The MIF(-/-) mice had prolonged hearing loss and significant loss of cochlear hair cells after intense noise exposure. Macrophage migration inhibitory factor may play an important role in recovery from acoustic trauma. Management of macrophage migration inhibitory factor may be a novel therapeutic option for noise-induced hearing loss.
Insights
Macrophage migration inhibitory factor (MIF) deficiency prolonged hearing loss and hair cell damage after noise exposure. MIF may be crucial for recovering from acoustic trauma and offers a potential therapeutic target for noise-induced hearing loss.
Area of Science:
- Ototolaryngology
- Immunology
- Cell Biology
Background:
- Macrophage migration inhibitory factor (MIF) is vital for neural development and expressed in the inner ear.
- Its specific role in auditory function, particularly in noise-induced hearing loss, is not well understood.
Purpose of the Study:
- To investigate the role of MIF in noise-induced hearing loss and cochlear damage.
- To determine if MIF deficiency exacerbates hearing impairment and hair cell loss following acoustic trauma.
Main Methods:
- Utilized MIF-deficient (MIF(-/-)) and wild-type mice exposed to octave band noise.
- Assessed auditory brainstem response thresholds, cochlear hair cell morphology via scanning electron microscopy, and cell apoptosis using TUNEL assay.
Main Results:
- Both mouse groups experienced significant hearing loss post-noise exposure.
- MIF(-/-) mice exhibited elevated hearing thresholds and greater outer hair cell damage 2 weeks after noise exposure compared to wild-type mice.
- TUNEL-positive cells, indicating apoptosis, were observed in the organ of Corti of MIF(-/-) mice.
Conclusions:
- MIF deficiency leads to prolonged hearing loss and cochlear hair cell loss after noise exposure.
- MIF appears to play a significant role in the recovery process from acoustic trauma.
- Modulating MIF levels could represent a novel therapeutic strategy for managing noise-induced hearing loss.

