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鼓室内载地塞米松水凝胶联合地塞米松洗脱耳蜗电极植入低创性豚鼠模型的长期效果和潜在局限性。

Long-term effects and potential limits of intratympanic dexamethasone-loaded hydrogels combined with dexamethasone-eluting cochlear electrodes in a low-insertion trauma Guinea pig model.

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.

Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.

出版信息

Hear Res. 2019 Dec;384:107825. doi: 10.1016/j.heares.2019.107825. Epub 2019 Oct 17.

Abstract

Cochlear implantation has become the most effective hearing restoration method and is one of the great advances in modern medicine. Early implants have been continuously developed into more efficient devices, and electro-acoustic stimulation is increasingly expanding the indication criteria for cochlear implants to patients with more residual hearing. Therefore, protecting the cochlear structures and maintaining its intrinsic capacities like residual hearing has become more important than ever before. In the present study, we aimed to assess the long-term protective effects of a dexamethasone-eluting electrode combined with the preoperative intratympanic application of a dexamethasone-loaded thermoreversible hydrogel in a cochlear implant guinea pig model. 40 normal-hearing animals were equally randomized into a control group receiving an unloaded hydrogel and a non-eluting electrode, a group receiving a dexamethasone-loaded hydrogel and a non-eluting electrode, a group receiving an unloaded hydrogel and a dexamethasone-eluting electrode and a group receiving both a dexamethasone-loaded hydrogel and a dexamethasone-eluting electrode. Residual hearing and impedances were investigated during a period of 120 days. Tissue response and histological changes of cochlear structures were analyzed at the end of the experiments. Treatment with dexamethasone did not show a significant protective effect on residual hearing independent of treatment group. Although the majority of the cochleae didn't exhibit any signs of electrode insertion trauma, a small degree of tissue response could be observed in all animals without a significant difference between the groups. Foreign body giant cells and osteogenesis were significantly associated with tissue response. Hair cells, synapsin-1-positive cells and spiral ganglion cells were preserved in all study groups. Cochlear implantation using a dexamethasone-eluting electrode alone and in combination with a dexamethasone-loaded hydrogel significantly protected auditory nerve fibers on day 120. Post-implantation impedances were equal across study groups and remained stable over the duration of the experiment. In this study we were able to show that use of a dexamethasone-eluting electrode alone and in combination with preoperative application of dexamethasone-loaded hydrogel significantly protects auditory nerve fibers. Furthermore, we have shown that a cochlear implantation-associated hearing threshold shift and tissue response may not be completely prevented by the sole application of dexamethasone.

摘要

人工耳蜗植入已成为最有效的听力恢复方法,也是现代医学的重大进步之一。早期的植入物不断发展为更高效的设备,电声刺激也在不断扩大人工耳蜗植入的适应证标准,适用于更多残余听力的患者。因此,保护耳蜗结构并维持其残余听力等内在能力比以往任何时候都更加重要。在本研究中,我们旨在评估地塞米松洗脱电极联合术前应用地塞米松负载热可逆水凝胶在耳蜗植入豚鼠模型中的长期保护作用。40 只正常听力动物被平均随机分为对照组(接受未负载水凝胶和非洗脱电极)、地塞米松负载水凝胶和非洗脱电极组、未负载水凝胶和地塞米松洗脱电极组以及地塞米松负载水凝胶和地塞米松洗脱电极组。在 120 天的时间内,我们研究了残余听力和阻抗。实验结束时,分析了耳蜗结构的组织反应和组织学变化。地塞米松治疗对残余听力没有显著的保护作用,与治疗组无关。尽管大多数耳蜗没有表现出电极插入创伤的迹象,但所有动物都观察到了一定程度的组织反应,但组间无显著差异。异物巨细胞和成骨与组织反应显著相关。所有研究组的毛细胞、突触素 1 阳性细胞和螺旋神经节细胞均得到保留。单独使用地塞米松洗脱电极和联合使用地塞米松负载水凝胶进行耳蜗植入在第 120 天显著保护听觉神经纤维。植入后的阻抗在各组之间是相等的,并在实验过程中保持稳定。在这项研究中,我们能够表明,单独使用地塞米松洗脱电极和联合使用术前应用地塞米松负载水凝胶可显著保护听觉神经纤维。此外,我们还表明,仅应用地塞米松并不能完全防止与耳蜗植入相关的听力阈值移位和组织反应。

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