Avian cochlear hair cell regeneration: stereological analyses of damage and recovery from a single high dose of gentamicin

• Published in: Hearing research 1995-12, Vol.92 (1), p.17-29
• Main Authors: Janas, Janice D., Cotanche, Douglas A., Rubel, Edwin W.
• Format: Article
• Language: English
• Subjects: Aminoglycoside otoxicity; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - toxicity; Autoradiography; Basilar Membrane - drug effects; Basilar Membrane - injuries; Basilar Membrane - ultrastructure; Basilar papilla; Biological and medical sciences; Cell Count - drug effects; Cell Survival - drug effects; Chickens; Chicks; Cochlea - drug effects; Cochlea - pathology; Cochlea - physiology; Cochlea - ultrastructure; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Fundamental and applied biological sciences. Psychology; Gentamicins - administration & dosage; Gentamicins - toxicity; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - pathology; Hair Cells, Auditory - physiology; Hair Cells, Auditory - ultrastructure; Injections, Subcutaneous; Isotope Labeling; Microscopy, Electron, Scanning; Nerve Regeneration; Regeneration; Thymidine - metabolism; Tritium - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/0378-5955(95)00190-5

Hair cell regeneration after acoustic trauma has been conclusively documented in birds. Previous studies of aminoglycoside ototoxicity have typically used 5–10 day courses of drug to damage the cochlea and trigger regeneration. This long-term lesion prevented analysis of the early events of regeneration. We set out to determine how much damage would occur and how recovery would proceed after a single high-dose injection of the aminoglycoside gentamicin. White Leghorn chicks were given a single high dose of gentamicin (100 mg/kg). Three post-injection survival groups with age-matched controls were studied: short-term (3–5 days), intermediate-term (2 weeks) and long-term (5 weeks). After sacrifice, cochleae were dissected and processed for scanning electron microscopy. Using stereological techniques, a quantitative analysis of cochlear hair cell counts along the proximal 50% of the cochlea was performed from scanning electron micrographs on 4–7 chicks from each group. Variable degrees of damage were seen 3–5 days after the drug injection. All hair cells were lost from the proximal 20% of the cochlea in all chicks. This complete hair cell loss could extend to 50% of the cochlea. Immature appearing hair cells could be first identified by their immature stereocilia at 3 days. Immature appearing hair cells were present in greatest number in regions which had been denuded of native hair cells and in regions where partial loss occurred. Interestingly, immature appearing hair cells also occasionally appeared in adjacent areas in which there was no apparent loss of native hair cells. Two-week survivors showed an elevation in hair cell number compared to controls in regions which had sustained damage and immediately adjacent regions. This elevation implies that an overproduction of hair cells might occur as part of the regeneration response. By 5 weeks after damage hair cell numbers approximated controls.