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


CONCLUSIONS
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.
Eshraghi
Adrien A
AA
Department of Otolaryngology, University of Miami Ear Institute, Miami, Florida 33136-1015, USA.
He
Jiao
J
Mou
Cai Hong
CH
Polak
Marek
M
Zine
Azel
A
Bonny
Christophe
C
Balkany
Thomas J
TJ
Van De Water
Thomas R
TR
D000704:Analysis of Variance; D000818:Animals; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003051:Cochlea / Q000293:injuries*; D019929:Cochlear Implantation / Q000009:adverse effects*; D004566:Electrodes / Q000009:adverse effects; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D034381:Hearing Loss / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009925:Organ of Corti / Q000187:drug effects; D017084:Otoacoustic Emissions, Spontaneous; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013997:Time Factors; D016896:Treatment Outcome
D010455:Peptides; D048031:JNK Mitogen-Activated Protein Kinases; C478085:D-JNKI-1