title: Cellular mechanisms of noise-induced hearing loss.
abstract: Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation.
authors.affiliation: Division of Otolaryngology, Department of Surgery, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA, 92093, United States.
authors.forename: Arwa
authors.initials: A
authors.lastname: Kurabi
authors.affiliation: Division of Otolaryngology, Department of Surgery, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA, 92093, United States.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Keithley
authors.affiliation: Division of Otolaryngology, Department of Surgery, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA, 92093, United States.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.affiliation: Division of Otolaryngology, Department of Surgery, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA, 92093, United States. Electronic address: afryan@ucsd.edu.
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.affiliation: Division of Otolaryngology, Department of Surgery, UCSD School of Medicine and San Diego VA Medical Center, La Jolla, CA, 92093, United States.
authors.forename: Ann C-Y
authors.initials: AC
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001305:Auditory Fatigue; D020013:Calcium Signaling; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006309:Hearing / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D009336:Necrosis; D009622:Noise / Q000009:adverse effects*; D018384:Oxidative Stress
keywords: Apoptosis; Damage signaling; Hair cell; Noise-induced hearing loss; Pharmacotherapy; Survival signaling