Otoprotective treatments against noise-induced cochlear neuropathy and associated hearing impairment

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dc.contributor.advisor Vlajkovic, S en
dc.contributor.author Fok, Christine en
dc.date.accessioned 2018-02-23T03:47:32Z en
dc.date.issued 2017 en
dc.identifier.uri http://hdl.handle.net/2292/36947 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Noise-induced hearing loss (NIHL) occurs as a result of acoustic overstimulation. Current treatments are limited to hearing loss management (hearing aids and cochlear implants), which cannot reverse cochlear injury. Hence, there is an urgent need to develop pharmacological interventions to rescue noise-induced cochlear injury. Previous studies in our laboratory have demonstrated the potential of adenosine A1 receptor agonists to ameliorate NIHL post-exposure. However, systemic administration of A1 receptor agonists may result in cardiovascular side effects. In this study, we investigated a novel treatment strategy targeting a molecular complex (neurabin/RGS4) that regulates adenosine A1 receptor signalling. Methods:Wistar rats were exposed to traumatic noise (8 – 16 kHz, 110 dB SPL) for 2 hours and treated with CCG-4986 (RGS4 inhibitor; 100 μM) 48 hours after noise exposure. The drug was delivered intratympanically onto the cochlear round window membrane using poloxamer-407 gel as a slow release medium. Auditory function was assessed using auditory brainstem responses (ABR) to tone pips (4 – 28 kHz). ABR thresholds and suprathreshold responses (wave I amplitudes and latencies at 4, 16 and 28 kHz) were analysed prior to and 16 days after noise exposure. Functional outcomes were correlated with quantitative histological assessments of sensory hair cell loss, and loss of afferent synapses and spiral ganglion neurons (SGN). Results: Intratympanic administration of CCG-4986 significantly attenuated ABR threshold shifts (10 – 20 dB) at frequencies above 4 kHz. The greatest effect was seen at frequencies corresponding to noise band (8 – 16 kHz). CCG-4986 also improved the amplitude and latency of ABR wave I, suggesting that the drug effectively reduced functional deficits in the cochleae exposed to traumatic noise. The rescue of auditory function correlated with histological outcomes. CCG-4986 treatment improved hair cell survival and ameliorated loss of afferent synapses in a turn-dependent manner, however it did not improve SGN survival. This study presents further evidence for the rescue potential of CCG-4986 in NIHL and related forms of sensorineural hearing loss. Further studies are required to determine its potential as a clinical otological treatment. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265061013802091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/nz/ en
dc.title Otoprotective treatments against noise-induced cochlear neuropathy and associated hearing impairment en
dc.type Thesis en
thesis.degree.discipline Biomedical Science en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 726385 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Te Kupenga Hauora Maori en
pubs.record-created-at-source-date 2018-02-23 en

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