Skip to main content

Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage

Abstract

Hair cells are sensory cells that transduce motion into neural signals. In the cochlea, they are used to detect sound waves in the environment and turn them into auditory signals that can be processed in the brain. Hair cells in the cochlea of birds and mammals were thought to be produced only during embryogenesis and, once made, they were expected to last throughout the lifetime of the animal. Thus, any loss of hair cells due to trauma or disease was thought to lead to permanent impairment of auditory function. Recently, however, studies from a number of laboratories have shown that hair cells in the avian cochlea can be regenerated after acoustic trauma or ototoxic drug damage. This regeneration is accompanied by a repair of the sensory organ and associated tissues and results in a recovery of auditory function. In this review, we examine and compare the structural events that lead to hair cell loss after noise damage and ototoxic drug damage as well as the processes involved in the recovery of the epithelium and the regeneration of the hair cells. Moreover, we examine functional recovery and how it relates to the structural recovery. Finally, we investigate the evidence for the hypothesis that supporting cells in the basilar papilla act as the progenitor cells for the regenerated hair cells and examine the cellular events required to stimulate the progenitor cells to leave the quiescent state, re-enter the cell cycle, and divide.

This is a preview of subscription content, access via your institution.

References

  1. Adler HJ, Kenealy JFX, DeDio RM, Saunders JC (1992) Threshold shift, hair cell loss, and hair bundle stiffness following exposure to 120 and 125 dB pure tones in the neonatal chick. Acta Otolaryngol (Stockh) 112:444–454

    Google Scholar 

  2. Adler HJ, Poje CP, Saunders JC (1993) Recovery of auditory function and structure in the chick after two intense pure tone exposures. Hear Res (in press)

  3. Anderson GJ, Legreid RJ, Saunders JC, Marsh RR (1989) Basilar papilla damage during intense sound exposure in the chick cochlea. Assoc Res Otolaryngol Abstr 12:219–220

    Google Scholar 

  4. Balak KJ, Corwin JT, Jones JE (1990) Regenerated hair cells can originate from supporting cell progeny: evidence from phototoxicity and laser ablation experiments in the lateral line system. J Neurosci 10:2502–2512

    Google Scholar 

  5. Baserga R (1985) The biology of cell reproduction. Harvard University Press, Cambridge, Mass

    Google Scholar 

  6. Becker H, Stanners CP, Kudlow JE (1971) Control of macromolecular synthesis in proliferating and resting Syrian hamster cells in monolayer culture. J Cell Physiol 77:43–50

    Google Scholar 

  7. Bohne BA (1976) Mechanisms of noise damage in the inner ear. In: Henderson D, Hamernik RP, Dosanjh DS, Mills JH (eds) Effects of noise on hearing. Raven Press, New York, pp 41–68

    Google Scholar 

  8. Brooks RF (1976) Regulation of the fibroblast cell cycle by serum. Nature 260:248–250

    Google Scholar 

  9. Campisi J, Pardee AB (1984) Post-translational control of the onset of DNA synthesis by an insulin-like growth factor. Mol Cell Biol 4:1807–1814

    Google Scholar 

  10. Cohen YE, Saunders JC (1993) The effects of sound overexposure on the spectral response patterns of nucleus magnocellularis in the neonatal chick. Exp Brain Res 95:202–212

    Google Scholar 

  11. Corwin JT (1981) Postembryonic production and aging of inner ear hair cells in sharks. J Comp Neurol 201:541–533

    Google Scholar 

  12. Corwin JT (1983) Postembryonic growth of the macula neglecta auditory detector in the ray, Raja clavata: continual increases in hair cell number, neural convergence, and physiological sensitivity. J Comp Neurol 217:345–356

    Google Scholar 

  13. Corwin JT (1985) Perpetual production of hair cells and maturational changes in hair cell ultrastructure accompany postembryonic growth in an amphibian ear. Proc Natl Acad Sci USA 82:3911–3915

    Google Scholar 

  14. Corwin JT, Cotanche DA (1988) Regeneration of sensory hair cells after acoustic trauma. Science 240:1772–1774

    Google Scholar 

  15. Corwin JT, Jones JE, Katayama A, Kelley MW, Warchol ME (1991) Hair cell regeneration: the identities of progenitor cells, potential triggers and instructive cues. In: Bock GR, Whelan J (eds) Regeneration of vertebrate sensory cells. Ciba Foundation Symposium 160. Wiley, New York, pp 103–130

    Google Scholar 

  16. Cotanche DA (1987a) Hair cell stereocilia regeneration in the chick cochlea after severe acoustic trauma. Assoc Res Otolaryngol Abstr 10:56

    Google Scholar 

  17. Cotanche DA (1987b) Regeneration of hair cell stereociliary bundles in the chick cochlea following severe acoustic trauma. Hear Res 30:181–196

    Google Scholar 

  18. Cotanche DA (1987c) Regeneration of the tectorial membrane in the chick cochlea following severe acoustic trauma. Hear Res 30:197–206

    Google Scholar 

  19. Cotanche DA (1992) Video-enhanced DIG images of the noise-damaged and regenerated chick tectorial membrane. Exp Neurol 115:23–26

    Google Scholar 

  20. Cotanche DA, Corwin JT (1991) Stereociliary bundles reorient during hair cell development and regeneration in the chick cochlea. Hear Res 52:379–402

    Google Scholar 

  21. Cotanche DA, Dopyera CEJ (1990) Hair cell and supporting cell response to acoustic trauma in the chick cochlea. Hear Res 46:29–40

    Google Scholar 

  22. Cotanche DA, Picard DA (1992) Progression of damage to the chick tectorial membrane with increased length of noise exposure. Assoc Res Otolaryngol Abstr 15:116

    Google Scholar 

  23. Cotanche DA, Sulik KK (1984) The development of stereociliary bundles in the cochlear duct of chick embryos. Dev Brain Res 16:181–193

    Google Scholar 

  24. Cotanche DA, Saunders JC, Tilney LG (1986) Hair cell recovery after severe acoustic trauma to the chick basilar papilla. Assoc Res Otolaryngol Abstr 9:14

    Google Scholar 

  25. Cotanche DA, Saunders JC, Tilney LG (1987) Hair cell damage produced by acoustic trauma in the chick cochlea. Hear Res 25:267–286

    Google Scholar 

  26. Cotanche DA, Petrell A, Picard DA (1991) Structural reorganization of hair cells and supporting cells during noise damage, recovery and regeneration in the chick cochlea. In: Bock GR, Whelan J (eds) Regeneration of vertebrate sensory cells. Ciba Foundation Symposium 160. Wiley, New York, pp 131–150

    Google Scholar 

  27. Covell WP (1953) Histological changes in the organ of Corti with intense sound. J Comp Neurol 99:43–60

    Google Scholar 

  28. Cruz RM, Lambert PR, Rubel EW (1985) Temporal patterns of gentamicin-induced hair cell loss in the chick basilar papilla. Otolaryngol Head Neck Surg 93[Special issue]:31

    Google Scholar 

  29. Cruz RM, Lambert PM, Rubel EW (1987) Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea. Arch Otolaryngol Head Neck Surg 113:1058–1062

    Google Scholar 

  30. Davis H, Derbyshire AJ, Kemp EH, Lurie MH, Upton M (1935) Experimental stimulation deafness. Science 81:101–103

    Google Scholar 

  31. Denhart DT, Edwards DR, Parfett CLJ (1986) Gene expression during the mammalian cell cycle. Biochim Biophys Acta 865:83–125

    Google Scholar 

  32. Duckert LG, Rubel EW (1990) Ultrastructural observations on regenerating hair cells in the chick basilar papilla. Hear Res 48:161–182

    Google Scholar 

  33. Duckert LG, Rubel EW (1993) Morphological correlates of functional recovery in the chicken inner ear after gentamicin treatment. J Comp Neurol 331:75–96

    Google Scholar 

  34. Eldredge DH, Covell WP (1958) A laboratory method for the study of acoustic trauma. Laryngoscope 68:465–486

    Google Scholar 

  35. Fischer FP (1992) Quantitative analysis of the innervation of the chicken basilar papilla. Hear Res 61:167–178

    Google Scholar 

  36. Fischer FP (1993) Quantitative TEM analysis of the barn owl basilar papilla. Hear Res (in press)

  37. Forge A, Li L, Corwin JT, Nevill G (1993) Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science 259:1616–1619

    CAS  PubMed  Google Scholar 

  38. Girod DA, Duckert LG, Rubel EW (1989) Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma. Hear Res 42:175–194

    Google Scholar 

  39. Girod DA, Tucci DL, Rubel EW (1991) Anatomical correlates of functional recovery in the avian inner ear following aminoglycoside ototoxicity. Laryngoscope 101:1139–1149

    Google Scholar 

  40. Gratzner HG (1982) Monoclonal antibody to 5-bromo-2-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218:474–475

    Google Scholar 

  41. Hashino E, Sokabe M (1989) Kanamycin induced low-frequency hearing loss in the budgerigar (Melopsittacus undulatus). J Acoust Soc Am 85:289–294

    Google Scholar 

  42. Hashino E, Sokabe M, Miyamoto K (1988) Frequency-specific susceptibility to acoustic trauma in the budgerigar (Melopsittacus undulatus) J Acoust Soc Am 83:2450–2453

    Google Scholar 

  43. Hashino E, Tanaka Y, Sokabe M (1991) Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea. Hear Res 52:356–368

    Google Scholar 

  44. Hashino E, TinHan E, Salvi RJ (1993) Base-to-apex gradient of DNA replication in the chick cochlear epithelium during kanamycin poisoning. Assoc Res Otolaryngol Abstr 16:104

    Google Scholar 

  45. Hashino E, Tanaka Y, Salvi RJ, Sokabe M (1992) Hair cell regeneration in the adult budgerigar after kanamycin ototoxicity. Hear Res 59:46–58

    Google Scholar 

  46. Henry WJ, Makaretz M, Saunders JC, Schneider ME, Vrettakos P (1988) Hair cell loss and regeneration after exposure to intense sound in neonatal chicks. Otolaryngol Head Neck Surg 98:607–611

    Google Scholar 

  47. Iurato S (1967) Vestibular labyrinth. In: Iurato S (eds) Submicroscopic structure of the inner ear. Pergamon Press, Oxford, pp 169–233

    Google Scholar 

  48. Janas JD, Cotanche DA, Rubel EW (1992) Avian cochlear hair cell regeneration: early response to aminoglycoside ototoxicity. Otolaryngol Head Neck Surg 107:233

    Google Scholar 

  49. Jones JE, Corwin JT (1993) Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity. J Neurosci 13:1022–1034

    Google Scholar 

  50. Katayama A, Corwin JT (1989) Cell production in the chicken cochlea. J Comp Neurol 281:129–135

    Google Scholar 

  51. Lajtha H (1963) On the concept of the cell cycle. J Cell Comp Physiol [Suppl] 62:143–145

    Google Scholar 

  52. LeFebvre PP, Malgrange B, Staecker H, Moonen G, Van De Water TR (1993) Retinoic acid stimulates regeneration of mammalian auditory hair cells. Science 260:692–695

    Google Scholar 

  53. Leof EB, Wyk JJ van, O'Keefe EJ, Pledger WJ (1983) Epidermal growth factor (EGF) is required only during the traverse of early G1 in PDGF-stimulated density-arrested BALB/c-3T3 cells. Exp Cell Res 147:202–208

    Google Scholar 

  54. Linzenbold A, Dooling RJ, Ryals BM (1993) A behavioral audibility curve for the Japanese quail (Coturnix coturnix japonica) Assoc Res Otolaryngol Abstr 16:53

    Google Scholar 

  55. Lippe WR, Westbrook EW, Ryals BM (1991) Hair cell regeneration in the chicken cochlea following aminoglycoside toxicity. Hear Res 56:203–210

    Google Scholar 

  56. Lombarte A, Yan HY, Popper AN, Chang JS, Platt C (1993) Damage and regeneration of hair cell ciliary bundles in a fish ear following treatment with gentamicin. Hear Res 64:166–174

    Google Scholar 

  57. Marean GC, Burt JM, Beecher MD, Rubel EW (1993) Hair cell regeneration in the European starling (Sturnus vulgaris): recovery of pure-tone detection thresholds. Hear Res (in press)

  58. Marsh RR, Xu L, Moy JP, Saunders JC (1990) Recovery of the basilar papilla following intense sound exposure in the chick. Hear Res 46:229–238

    Google Scholar 

  59. McFadden EA, Saunders JC (1989) Recovery of auditory function following intense sound exposure in the neonatal chick. Hear Res 41:205–216

    Google Scholar 

  60. Niemiec AJ, Raphael Y, Moody DB (1993) Return of auditory function following structural regeneration after acoustic trauma: behavioral measures from quail. Hear Res (in press)

  61. Oesterle EC, Cunningham DE, Rubel EW (1992) Ultrastructure of hyaline, border, and vacuole cells in chick inner ear. J Comp Neurol 318:64–82

    Google Scholar 

  62. Pardee AB (1974) A restriction point for control of normal animal cell proliferation. Proc Natl Acad Sci USA 71:1286–1290

    Google Scholar 

  63. Pardee AB (1987) Molecules involved in proliferation of normal and cancer cells. Presidential address. Cancer Res 47:1488–1491

    Google Scholar 

  64. Pardee AB (1989) G1 events and regulation of cell proliferation. Science 246:603–608

    Google Scholar 

  65. Picard DA, Cotanche DA (1990) Tall hair cells in the chick cochlea show hypersensitivity to anoxia, as revealed by localized apical blebbing during fixation. Assoc Res Otolaryngol Abstr 13:384

    Google Scholar 

  66. Pines J (1992) Cell proliferation and control. Curr Opin Cell Biol 4:144–148

    Google Scholar 

  67. Pledger WJ, Stiles CD, Antoniades HN, Scher CD (1977) Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci USA 74:4481–4485

    Google Scholar 

  68. Pledger WJ, Stiles CD, Antoniades HN, Scher CD (1978) An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci USA 75:2839–2843

    Google Scholar 

  69. Pugliano FA, Pribitikin E, Adler HJ, Saunders JC (1993a) Growth of evoked potential amplitude in neonatal chicks exposed to intense sound. Acta Otolaryngol 113:18–25

    Google Scholar 

  70. Pugliano FA, Wilcox TO, Rossiter J, Saunders JC (1993b) Recovery of auditory structure and function in neonatal chicks exposed to intense sound for 8 days. Neurosci Lett 151:214–218

    Google Scholar 

  71. Raphael Y (1991) Damage to the tectorial membrane may protect chick hair cells from noise overstimulation. Hear Res 53:173–184

    Google Scholar 

  72. Raphael Y (1992) Evidence for supporting cell mitosis in response to acoustic trauma in the avian inner ear. J Neurocytol 21:663–671

    Google Scholar 

  73. Raphael Y (1993) Reorganization of the chick basilar papilla after acoustic trauma. J Comp Neurol 330:521–532

    Google Scholar 

  74. Roberson DW, Rubel EW (1993) Autoradiographic labeling in the regenerating avian cochlea after continuous intralabyrinthine infusion of tritiated thymidine. Assoc Res Otolaryngol Abstr 16:104

    Google Scholar 

  75. Rossow PW, Riddle VGH, Pardee AB (1979) Synthesis of labile, serum-dependent protein in early G1 controls animal cell growth. Proc Natl Acad Sci USA 76:4446–4450

    Google Scholar 

  76. Rubel EW, Ryals BM (1982) Patterns of hair cell loss in chick basilar papilla after intense auditory stimulation. Acta Otolaryngol (Stockh) 93:31–41

    Google Scholar 

  77. Rubel EW, Ryals BM (1983) Development of the place principle: acoustic trauma. Science 219:512–514

    Google Scholar 

  78. Rubel EW, Oesterle EC, Weisleder P (1991) Hair cell regeneration in the avian inner ear. In: Bock GR, Whelan J (eds) Regeneration of vertebrate sensory cells. Ciba Foundation Symposium 160. Wiley, New York, pp 77–102

    Google Scholar 

  79. Ruben RJ (1967) Development of the inner ear of the mouse. A radioautographic study of terminal mitosis. Acta Otolaryngol (Stockh) [Suppl] 220:1–44

    Google Scholar 

  80. Ryals BM, Rubel EW (1982) Patterns of hair cell loss in the chick basilar papilla after intense auditory stimulation: frequency organization. Acta Otolaryngol (Stockh) 93:205–210

    Google Scholar 

  81. Ryals BM, Rubel EW (1988) Hair cell regeneration after acoustic trauma in adult Coturnix quail. Science 240:1774–1776

    Google Scholar 

  82. Ryals BM, Westbrook EW (1990) Hair cell regeneration in senescent quail. Hear Res 50:87–96

    Google Scholar 

  83. Ryals BM, Westbrook EW (1993) TEM analysis of neural terminals on autoradiographically identified regenerated hair cells. Hear Res (in press)

  84. Ryals BM, Westbrook EW, Stoots S, Spencer RF (1992) Changes in the acoustic nerve after hair cell regeneration. Exp Neurol 115:18–22

    Google Scholar 

  85. Saunders JC, Dear SD, Schneider ME (1985) The anatomical consequences of acoustic injury: a review and tutorial. J Acoust Soc Am 78:833–860

    Google Scholar 

  86. Saunders JC, Adler HJ, Pugliano FA (1992) The structural and functional aspects of hair cell regeneration in the chick as a result of exposure to intense sound. Exp Neurol 115:13–17

    Google Scholar 

  87. Saunders JC, Torsiglieri AJ, DeDio RM (1993) The growth of hearing loss in neonatal chicks exposed to intense pure tones. Hear Res 69:25–34

    Google Scholar 

  88. Saunders SS, Salvi RJ, Chen L, Turgen N (1993) Psychacoustic measures of recovery from noise-induced hearing loss in adult chickens. Assoc Res Otolaryngol Abstr 16:152

    Google Scholar 

  89. Stiles CD, Isberg RR, Pledger WJ, Antoniades HN, Scher CD (1979) Control of the BALB/c-3T3 cell cycle by nutrients and serum growth factors: analysis using platelet-derived growth factor and platelet-poor plasma. J Cell Physiol 99:395–406

    Google Scholar 

  90. Stone JS, Cotanche DA (1992) Synchronization of hair cell regeneration in the chick cochlea following noise damage. J Cell Sci 102:671–680

    Google Scholar 

  91. Stone JS, Cotanche DA (1993a) Identification of the timing of S phase and the patterns of cell proliferation during hair cell regeneration in the chick cochlea. J Comp Neurol (in press)

  92. Stone JS, Cotanche DA (1993b) Patterns of cell division during hair cell regeneration in the chick cochlea. Assoc Res Otolaryngol Abstr 16:104

    Google Scholar 

  93. Takasaka T, Smith CA (1971) The structure and innervation of the pigeon's basilar papilla. J Ultrastruct Res 35:20–65

    Google Scholar 

  94. Tanaka K, Smith CA (1978) Structure of the chicken's inner ear: SEM and TEM study. Am J Anat 153:251–272

    Google Scholar 

  95. Tilney LG, Saunders JC (1983) Actin filaments, stereocilia and hair cells of the bird cochlea. I. The length, number, width and distribution of stereocilia of each hair cell are related to the position of the hair cell on the cochlea. J Cell Biol 96:807–821

    Google Scholar 

  96. Tilney LG, Tilney MS, Saunders JC, DeRosier DJ (1986) Actin filaments, stereocilia, and hair cells of the bird cochlea. III. The development and differentiation of hair cells and stereocilia in embryos. Dev Biol 116:100–118

    Google Scholar 

  97. Tilney LG, Tilney MS, Cotanche DA (1988) Actin filaments, stereocilia and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated. J Cell Biol 106:355–365

    Google Scholar 

  98. Tucci DL, Rubel EW (1990) Physiological status of regenerated hair cells in the avian inner ear following aminoglycoside ototoxicity. Otolaryngol Head Neck Surg 103:443–450

    Google Scholar 

  99. Warchol ME, Corwin JT (1992) Hair cell regeneration in vitro: determination of the latency and pattern of cell proliferation. Assoc Res Otolaryngol Abstr 15:106

    Google Scholar 

  100. Warchol ME, Lambert PR, Goldstein BJ, Forge A, Corwin JT (1993) Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. Science 259:1619–1622

    CAS  PubMed  Google Scholar 

  101. Weisleder P, Rubel EW (1993) Hair cell regeneration after streptomycin toxicity in the avian vestibular epithelium. J Comp Neurol 331:97–110

    Google Scholar 

  102. Wharton W, Leof E, Pledger WJ, O'Keefe EJ (1982) Modulation of the epidermal growth factor receptor by platelet-derived growth factor and choleragen: effects on mitogenesis. Proc Natl Acad Sci USA 79:5567–5571

    Google Scholar 

  103. Yang HC, Pardee AB (1986) Insulin-like growth factor I regulation of transcription and replicating enzyme induction necessary for DNA synthesis. J Cell Physiol 127:410–416

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Douglas A. Cotanche.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cotanche, D.A., Lee, K.H., Stone, J.S. et al. Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage. Anat Embryol 189, 1–18 (1994). https://doi.org/10.1007/BF00193125

Download citation

Key words

  • Hair cell
  • Regeneration
  • Avian
  • Progenitor cells
  • Basilar papilla