The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotective strategies

Thomas R. Van de Water, Ralph N. Abi-Hachem, Azel Zine

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

One of the causes of sensorineural hearing loss is the loss of auditory hair cells following exposure to environmental stresses. Auditory hair cell death in response to cochlear trauma occurs via both necrosis and apoptosis. Apoptosis of hair cells involves the caspase and MAPK/JNK pathways which are activated by oxidative stress and secretion of inflammatory cytokines in response to trauma. Identification of the pathways that lead to apoptosis provides therapeutic targets for the conservation of hearing. Antioxidants reduce the level of reactive oxygen species and reactive nitrogen species generated by oxidative stress in response to acoustic trauma, aminoglycoside and platinum-based drugs. Caspase inhibitors affect both the extrinsic and intrinsic apoptotic pathways, thereby reducing cisplatin, aminoglycoside, hydraulic trauma and ischemia-induced hearing losses. Corticosteroid therapy reduces inflammation and inhibits apoptosis while activating pro-survival pathways in the organ of Corti following exposure to noise, vibration, cisplatin, aminoglycoside, ischemia/reperfusion injury, bacterial meningitis and electrode insertion trauma. Inhibitors of JNK signaling pathway prevent apoptosis of auditory hair cells following electrode insertion trauma, acute labyrinthitis, acoustic trauma and aminoglycoside ototoxicity.

Original languageEnglish (US)
Pages (from-to)147-163
Number of pages17
JournalRecent Patents on CNS Drug Discovery
Volume5
Issue number2
DOIs
StatePublished - Jun 28 2010

Keywords

  • Antioxidants
  • Apoptosis
  • Auditory hair cells
  • C-jun n-terminal kinase
  • Caspase
  • Cochlea
  • Cochlear implantation
  • Corticosteroids
  • Inflammation
  • Otoprotection
  • Ototoxicity
  • Sensorineural hearing loss
  • Trauma

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Drug Discovery

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