Vink Henk A, van Dorp Willem C, Thomeer Hans G X M, Versnel Huib, Ramekers Dyan
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.
UMC Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Brain Sci. 2020 Oct 28;10(11):787. doi: 10.3390/brainsci10110787.
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.
在使用人工耳蜗（CI）恢复听力的聋人受试者中，听神经会发生退化，这可能会对CI的有效性产生负面影响。这种神经退化可以通过神经营养治疗来减轻。在这里，我们比较了天然存在的酪氨酸受体激酶B（TrkB）激动剂脑源性神经营养因子（BDNF）和小分子TrkB激动剂7,8,3'-三羟基黄酮（THF）对耳聋豚鼠听神经的保护作用。由于具有更好的药代动力学特性，THF在整个耳蜗中可能比BDNF更有效。神经营养化合物通过在穿孔圆窗膜上放置明胶海绵来递送。为了补充螺旋神经节细胞（SGC）的组织学研究，在治疗开始四周后进行电诱发复合动作电位（eCAP）记录。我们分析了eCAP相间间隙（IPG）效应以及从脉冲序列诱发的eCAP得出的测量值，这两者都表明SGC的健康状况。与未治疗的对照组相比，BDNF而非THF使耳蜗基部转弯处的SGC存活率显著更高。关于IPG效应和脉冲序列反应，BDNF治疗的动物比未治疗和THF治疗的动物表现出更正常的反应。因此，我们证实了BDNF的保护作用，但我们尚未通过我们临床适用的递送方法证实先前报道的THF的保护作用。
