Murine cochlear damage models in the context of hair cell regeneration research

• Published in: Hearing research Vol. 447; p. 109021
• Main Authors: Maraslioglu-Sperber, Ayse, Blanc, Fabian, Heller, Stefan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2024
• Subjects: Acoustic Stimulation; Animals; Cochlea - pathology; Cochlea - physiopathology; Disease Models, Animal; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - pathology; Hearing; Hearing Loss - pathology; Hearing Loss - physiopathology; Hearing Loss, Noise-Induced - pathology; Hearing Loss, Noise-Induced - physiopathology; Humans; Mice; Regeneration
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2024.109021

•Advantages and disadvantages of existing hair cell ablation methods in mice.•Limitations of existing approaches for use in hair cell regenerative studies.•Outlook on existing gaps where refinement of damage models would be beneficial.
Understanding the complex pathologies associated with hearing loss is a significant motivation for conducting inner ear research. Lifelong exposure to loud noise, ototoxic drugs, genetic diversity, sex, and aging collectively contribute to human hearing loss. Replicating this pathology in research animals is challenging because hearing impairment has varied causes and different manifestations. A central aspect, however, is the loss of sensory hair cells and the inability of the mammalian cochlea to replace them. Researching therapeutic strategies to rekindle regenerative cochlear capacity, therefore, requires the generation of animal models in which cochlear hair cells are eliminated. This review discusses different approaches to ablate cochlear hair cells in adult mice. We inventoried the cochlear cyto- and histo-pathology caused by acoustic overstimulation, systemic and locally applied drugs, and various genetic tools. The focus is not to prescribe a perfect damage model but to highlight the limitations and advantages of existing approaches and identify areas for further refinement of damage models for use in regenerative studies.