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脂肪来源基质细胞移植可保护人工耳蜗植入模型中听觉神经的功能和形态完整性。

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation.

作者信息

Radeloff Andreas, Nada Nashwa, El Mahallawi Trandil, Kolkaila Enaas, Vollmer Maike, Rak Kristen, Hagen Rudolf, Schendzielorz Philipp

机构信息

Division of Oto-Rhino-Laryngology, Head and Neck Surgery, Carl von Ossietzky-University.

Cluster of excellence "Hearing 4 All".

出版信息

Neuroreport. 2021 Jun 9;32(9):776-782. doi: 10.1097/WNR.0000000000001651.

Abstract

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects.

摘要

人工耳蜗被认为是重度听力损失和失聪患者的金标准治疗方法。人工耳蜗绕过受损的毛细胞,直接刺激听神经的螺旋神经节神经元(SGNs)。因此,功能性SGNs的存在对于人工耳蜗电刺激听力中的言语感知至关重要。在失聪个体中,由于缺乏通常由内耳感觉细胞提供的神经营养支持,SGNs会逐渐退化。脂肪来源的基质细胞(ASCs)已知能产生神经营养因子。在一个感觉性听力损失和人工耳蜗植入的豚鼠模型中,在一侧植入人工耳蜗之前,将自体ASCs移植到鼓阶。人工耳蜗植入8周后记录电诱发听性脑干反应(eABR)。在实验结束时,对耳蜗进行组织学评估。与未治疗的对照动物相比,ASCs移植导致SGNs及其周围神经突数量增加。在ASCs移植的动物中,平均eABR阈值较低,阈上振幅较大,表明完整听神经纤维数量较多。此外,与对照组相比,ASCs移植动物的eABR振幅-强度函数在响应增加的相间间隙(IPGs)时显示出更陡的斜率,表明听神经功能更好。总之,结果表明将自体ASCs移植到失聪内耳可能对SGNs及其周围神经突的存活具有保护作用,从而可能有助于人工耳蜗植入患者在言语辨别性能方面获得长期益处。

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