D-JNKI-1 treatment prevents the progression of hearing loss in a model of cochlear implantation trauma

Otol Neurotol. 2006 Jun;27(4):504-11. doi: 10.1097/01.mao.0000217354.88710.13.

Abstract

Hypotheses: 1) Hearing loss caused by electrode insertion trauma has both acute and delayed components; and 2) the delayed component of trauma-initiated hearing loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after the electrode insertion within the cochlea.

Background: Acute trauma to the macroscopic elements of the cochlea from electrode insertion is well known. The impact of trauma-induced oxidative stress within injured cochlear tissues and the efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is not well defined.

Methods: Hearing function was tested by pure-tone evoked auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was delivered into the scala tympani immediately after electrode trauma and for 7 days. Controls were nontreated contralateral and D-JNKI-1-treated ears without electrode insertion trauma.

Results: There was no increase in the hearing thresholds of either the contralateral control ears or in the D-JNKI-1 without trauma animals. There was a progressive increase in ABR thresholds and decrease in DPOAE amplitudes after electrode insertion trauma in untreated and in AP-treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in ABR thresholds and decrease in DPOAE amplitudes that occur after electrode insertion trauma.

Conclusion: Hearing loss caused by cochlear implant electrode insertion trauma in guinea pigs has both acute and delayed components. The delayed component can be prevented by treating the cochlea with D-JNKI-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Audiometry, Pure-Tone
  • Auditory Threshold / drug effects
  • Cell Death / drug effects
  • Cochlea / injuries*
  • Cochlear Implantation / adverse effects*
  • Electrodes / adverse effects
  • Evoked Potentials, Auditory, Brain Stem
  • Guinea Pigs
  • Hearing Loss / etiology
  • Hearing Loss / prevention & control*
  • Hearing Loss / therapy
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Organ of Corti / drug effects
  • Otoacoustic Emissions, Spontaneous
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Random Allocation
  • Time Factors
  • Treatment Outcome

Substances

  • Peptides
  • JNK Mitogen-Activated Protein Kinases
  • D-JNKI-1