Evidence for a dynorphin-mediated inner ear immune/inflammatory response and glutamate-induced neural excitotoxicity: An updated analysis

Tony L. Sahley, David J. Anderson, Michael D. Hammonds, Karthik Chandu, Frank E. Musiek

Research output: Contribution to journalReview article

Abstract

Acoustic overstimulation (AOS) is defined as the stressful overexposure to high-intensity sounds. AOS is a precipitating factor that leads to a glutamate (GLU)-induced Type I auditory neural excitotoxicity and an activation of an immune/inflammatory/ oxidative stress response within the inner ear, often resulting in cochlear hearing loss. The dendrites of the Type I auditory neural neurons that innervate the inner hair cells (IHCs), and respond to the IHC release of the excitatory neurotransmitter GLU, are themselves directly innervated by the dynorphin (DYN)-bearing axon terminals of the descending brain stem lateral olivocochlear (LOC) system. DYNs are known to increase GLU availability, potentiate GLU excitotoxicity, and induce superoxide production. DYNs also increase the production of proinflammatory cytokines by modulating immune/inflammatory signal transduction pathways. Evidence is provided supporting the possibility that the GLU-mediated Type I auditory neural dendritic swelling, inflammation, excitotoxicity, and cochlear hearing loss that follow AOS may be part of a brain stem-activated, DYN-mediated cascade of inflammatory events subsequent to a LOC release of DYNs into the cochlea. In support of a DYN-mediated cascade of events are established investigations linking DYNs to the immune/inflammatory/excitotoxic response in other neural systems.

Original languageEnglish (US)
Pages (from-to)1421-1460
Number of pages40
JournalJournal of neurophysiology
Volume122
Issue number4
DOIs
StatePublished - 2019

Keywords

  • Acoustic overstimulation
  • Dynorphins
  • Glutamate excitotoxicity
  • Immune/inflammatory system
  • Lateral olivocochlear system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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