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

Adrien A. Eshraghi, Jiao He, Cai Hong Mou, Marek Polak, Azel Zine, Christophe Bonny, Thomas J. Balkany, Thomas R. Van De Water

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)504-511
Number of pages8
JournalOtology and Neurotology
Volume27
Issue number4
DOIs
StatePublished - Jun 1 2006

Keywords

  • c-Jun N-terminal Kinase
  • Cochlear Implantation
  • D-JNKI-1 Inhibitory Peptide
  • Electrode Trauma-initiated Apoptosis
  • Hearing Preservation
  • Oxidative Stress

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Neuroscience(all)

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