慢性电刺激下的人工耳蜗植入鼠模型。
A mouse model of cochlear implantation with chronic electric stimulation.
机构信息
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA, United States of America.
Cochlear Americas, Centennial, CO, United States of America.
出版信息
PLoS One. 2019 Apr 18;14(4):e0215407. doi: 10.1371/journal.pone.0215407. eCollection 2019.
OBJECTIVES
Cochlear implants provide an effective treatment option for those with severe hearing loss, including those with preserved low frequency hearing. However, certain issues can reduce implant efficacy including intracochlear tissue response and delayed loss of residual acoustic hearing. We describe a mouse model of cochlear implantation with chronic electric stimulation that can be used to study cochlear implant biology and related pathologies.
METHODS
Twelve normal hearing adult CBA/J mice underwent unilateral cochlear implantation and were evenly divided into one group receiving electric stimulation and one not. Serial impedance and neural response telemetry (NRT) measurements were made to assess implant functionality. Functionality was defined as having at least one electrode with an impedance ≤ 35 kOhms. Mouse cochleae were harvested for histology and 3D x-ray microscopy 21 days post-operatively, or, in case the implant was still functional, at a later time point when the implant failed. A separate experiment measured the hearing preservation rate in 7 adult CBA/J mice undergoing unilateral cochlear implantation with serial auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE).
RESULTS
Implants maintained functionality for a mean of 35 days in the non-stimulated group and 19.8 days in the stimulated group. Reliable NRT and behavioral responses to electric stimulation were recorded. A robust intracochlear peri-implant tissue response with neo-ossification was seen in all cochleae. Six of seven mice maintained intact low frequency hearing up to 6 weeks following cochlear implantation.
CONCLUSIONS
We demonstrate the feasibility of cochlear implantation and behaviorally significant electric stimulation in the mouse, with the potential for hearing preservation. This model may be combined with established mouse models of hearing loss and the large genetic and molecular research toolkit unique to the mouse for mechanistic and therapeutic investigations of cochlear implant biology.
目的
人工耳蜗为重度听力损失患者（包括低频残余听力保留的患者）提供了一种有效的治疗选择。然而，某些问题会降低植入物的功效，包括耳蜗内组织反应和残余听觉的延迟丧失。我们描述了一种具有慢性电刺激的耳蜗植入小鼠模型，可用于研究人工耳蜗生物学和相关病理学。
方法
12 只正常听力的成年 CBA/J 小鼠接受单侧耳蜗植入，并平均分为接受电刺激组和未接受电刺激组。进行连续阻抗和神经反应遥测（NRT）测量以评估植入物的功能。功能定义为至少有一个电极的阻抗≤35kΩ。术后 21 天或在植入物失效时，如果植入物仍然有功能，则对小鼠耳蜗进行组织学和 3D X 射线显微镜检查。在 7 只成年 CBA/J 小鼠中进行了单侧耳蜗植入，并用听性脑干反应（ABR）和畸变产物耳声发射（DPOAE）进行了连续听觉保留率测量。
结果
在未刺激组中，植入物的功能平均维持了 35 天，在刺激组中维持了 19.8 天。记录到可靠的 NRT 和对电刺激的行为反应。所有耳蜗均出现了强烈的耳蜗内植入物周围组织反应和新生骨化。在耳蜗植入后 6 周内，6/7 只小鼠保持了低频听力的完整。
结论
我们证明了在小鼠中进行耳蜗植入和具有行为意义的电刺激的可行性，同时具有听力保护的潜力。该模型可以与已建立的听力损失小鼠模型以及小鼠特有的大型遗传和分子研究工具包相结合，用于人工耳蜗生物学的机制和治疗研究。
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