Honeder Clemens, Zhu Chengjing, Gausterer Julia Clara, Schöpper Hanna, Ahmadi Navid, Saidov Nodir, Nieratschker Michael, Gabor Franz, Arnoldner Christoph
Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
Audiol Neurootol. 2019;24(5):237-244. doi: 10.1159/000501331. Epub 2019 Oct 1.
In recent years, the preservation of residual hearing has become a major factor in patients undergoing cochlear implantation (CI). In studies attempting to pharmaceutically improve hearing preservation rates, glucocorticoids (GCs) applied perioperatively in many institutions have emerged as a promising treatment regimen. Although dexamethasone is most commonly used and has been applied successfully by various research groups, recently pharmacological properties have been reported to be relatively unsuitable for topical delivery to the inner ear. Consequently other glucocorticoids merit further evaluation. The aim of this study was therefore to evaluate the otoprotective effects of the topical application of a sustained-release triamcinolone acetonide (TAAC) hydrogel in CI with hearing preservation.
Normal-hearing pigmented guinea pigs were randomized into a group receiving a single dose of a 6% TAAC poloxamer 407 hydrogel, a group receiving a 30% TAAC hydrogel and a control group. All hydrogel applications were performed 1 day prior to CI. After a cochleostomy was drilled, a specifically designed silicone electrode was inserted into the scala tympani for 5 mm. Frequency-specific compound action potentials of the auditory nerve (0.5-32 kHz) were measured pre- and directly postoperatively as well as on days 3, 7, 14, 21, and 28. Finally, temporal bones were harvested for histological evaluation.
Application of the TAAC hydrogels resulted in significantly reduced hearing threshold shifts in low, middle and high frequencies and improved spiral ganglion cell survival in the second turn of the cochlea. Outer hair cell numbers in the basal and second turn of the cochlea were slightly reduced after TAAC application.
In summary, we were able to demonstrate functional benefits of a single preoperative application of a TAAC hydrogel in a guinea pig model for CI, which persisted until the end of the observational period, that is, 28 days after surgery.
近年来,保留残余听力已成为接受人工耳蜗植入(CI)患者的一个主要因素。在试图通过药物提高听力保留率的研究中,许多机构围手术期应用的糖皮质激素(GCs)已成为一种有前景的治疗方案。尽管地塞米松是最常用的,并且已被多个研究小组成功应用,但最近有报道称其药理特性相对不适合内耳局部给药。因此,其他糖皮质激素值得进一步评估。因此,本研究的目的是评估在人工耳蜗植入中局部应用缓释曲安奈德(TAAC)水凝胶对听力保留的耳保护作用。
将听力正常的有色豚鼠随机分为接受单剂量6%TAAC泊洛沙姆407水凝胶的组、接受30%TAAC水凝胶的组和对照组。所有水凝胶应用均在人工耳蜗植入前1天进行。在钻开蜗窗后,将专门设计的硅胶电极插入鼓阶5毫米。在术前、术后即刻以及术后第3、7、14、21和28天测量听神经的频率特异性复合动作电位(0.5 - 32千赫)。最后,获取颞骨进行组织学评估。
TAAC水凝胶的应用导致低频、中频和高频听力阈值变化显著降低,并改善了耳蜗第二圈螺旋神经节细胞的存活。应用TAAC后,耳蜗基底圈和第二圈的外毛细胞数量略有减少。
总之,我们能够在豚鼠人工耳蜗植入模型中证明术前单次应用TAAC水凝胶的功能益处,这种益处一直持续到观察期结束,即术后28天。