Sustained-Release Triamcinolone Acetonide Hydrogels Reduce Hearing Threshold Shifts in a Model for Cochlear Implantation with Hearing Preservation

C. Honeder, Chengjing Zhu, J. Gausterer, H. Schöpper, N. Ahmadi, Nodir Saidov, Michael Nieratschker, F. Gabor, C. Arnoldner
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引用次数: 7

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.
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缓释曲安奈德水凝胶在保留听力的人工耳蜗植入模型中降低听力阈值移位
近年来,保留残余听力已成为人工耳蜗植入术患者的主要考虑因素。在试图从药物上提高听力保有率的研究中,糖皮质激素(GCs)在许多机构的围手术期应用已成为一种有前途的治疗方案。尽管地塞米松是最常用的药物,并且已被多个研究小组成功应用,但最近有报道称其药理性质相对不适合局部内耳给药。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缓释曲安奈德(TAAC)水凝胶局部应用于具有听力保护的CI患者的耳保护作用。方法:将听力正常的豚鼠随机分为单剂量6% TAAC波洛沙姆407水凝胶组、30% TAAC波洛沙姆407水凝胶组和对照组。所有水凝胶应用于CI前1天。钻孔耳蜗造口后,将一个专门设计的硅胶电极插入鼓室5毫米。在术前、术后以及第3、7、14、21、28天分别测量听神经频率特异性复合动作电位(0.5 ~ 32khz)。最后,取颞骨进行组织学评估。结果:应用TAAC水凝胶可显著降低低、中、高频听阈偏移,提高第二轮耳蜗螺旋神经节细胞存活率。应用TAAC后,耳蜗基部和第二匝外毛细胞数量略有减少。结论:总之,我们能够证明在豚鼠CI模型中术前应用TAAC水凝胶的功能益处,这种益处持续到观察期结束,即手术后28天。
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