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Open AccessFeature PaperArticle

BDNF Outperforms TrkB Agonist 7,8,3′-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs

1
Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Utrecht University, Room G.02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
2
UMC Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(11), 787; https://doi.org/10.3390/brainsci10110787
Received: 30 September 2020 / Revised: 23 October 2020 / Accepted: 27 October 2020 / Published: 28 October 2020
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor in the Auditory System)
In deaf subjects using a cochlear implant (CI) for hearing restoration, the auditory nerve is subject to degeneration, which may negatively impact CI effectiveness. This nerve degeneration can be reduced by neurotrophic treatment. Here, we compare the preservative effects of the naturally occurring tyrosine receptor kinase B (TrkB) agonist brain-derived neurotrophic factor (BDNF) and the small-molecule TrkB agonist 7,8,3′-trihydroxyflavone (THF) on the auditory nerve in deafened guinea pigs. THF may be more effective than BDNF throughout the cochlea because of better pharmacokinetic properties. The neurotrophic compounds were delivered by placement of a gelatin sponge on the perforated round window membrane. To complement the histology of spiral ganglion cells (SGCs), electrically evoked compound action potential (eCAP) recordings were performed four weeks after treatment initiation. We analyzed the eCAP inter-phase gap (IPG) effect and measures derived from pulse-train evoked eCAPs, both indicative of SGC healthiness. BDNF but not THF yielded a significantly higher survival of SGCs in the basal cochlear turn than untreated controls. Regarding IPG effect and pulse-train responses, the BDNF-treated animals exhibited more normal responses than both untreated and THF-treated animals. We have thus confirmed the protective effect of BDNF, but we have not confirmed previously reported protective effects of THF with our clinically applicable delivery method. View Full-Text
Keywords: cochlea; hearing loss; neurodegeneration; spiral ganglion cell; eCAP; IPG effect; neuroprotection; neurotrophic factor; neurostimulation; small molecule cochlea; hearing loss; neurodegeneration; spiral ganglion cell; eCAP; IPG effect; neuroprotection; neurotrophic factor; neurostimulation; small molecule
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Vink, H.A.; van Dorp, W.C.; Thomeer, H.G.X.M.; Versnel, H.; Ramekers, D. BDNF Outperforms TrkB Agonist 7,8,3′-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs. Brain Sci. 2020, 10, 787.

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