Research Article: A mouse model of cochlear implantation with chronic electric stimulation

Date Published: April 18, 2019

Publisher: Public Library of Science

Author(s): Alexander D. Claussen, René Vielman Quevedo, Brian Mostaert, Jonathon R. Kirk, Wolfram F. Dueck, Marlan R. Hansen, Adrien A. Eshraghi.

http://doi.org/10.1371/journal.pone.0215407

Abstract

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.

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).

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.

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.

Partial Text

Cochlear implants (CI) have been established as a safe and effective strategy treating severe to profound sensorineural hearing loss in both adults and children. Advances in electrode design and ‘soft’ surgical techniques have enabled combined electrical and acoustic stimulation in many patients with functional low frequency hearing, which brings improved music perception [1, 2], speech in noise understanding [3–5] and sound localization [6, 7]. The ability to implant patients with intact low frequency hearing has greatly expanded the potential CI candidate population, which by 2020 in the USA is estimated to reach 1.51 and 1.92 million people for hearing preservation (e.g. Hybrid) and conventional CIs, respectively [8].

This study demonstrates the technical feasibility of mouse cochlear implantation with chronic electric stimulation, and the ability of hearing preservation surgery. Overall, 8/12 subjects maintained one or more functioning electrodes for at least 3 weeks, enabling electric stimulation over the same time period. Behavioral responses to electric stimulation and objective measures (NRT) evidenced successful stimulation of the mouse auditory system. Further, the surgery and experimental procedures were well tolerated by mice without any signs of vestibulopathy or implant related complications.

We describe a mouse model of cochlear implantation with chronic electric stimulation and the potential for hearing preservation implantation. The intracochlear tissue response seen in some human temporal bones is robustly reproduced in the CBA/J mouse, which may allow future mechanistic and therapeutic studies. The molecular and genetic research techniques available to the mouse, in addition to the radiologic, histologic and objective measures methods described here, provides unique advantages over other model species to CI biology investigations. Future studies with this model should employ established mouse models of hearing loss to more closely mirror human cochlear implantation recipients.

 

Source:

http://doi.org/10.1371/journal.pone.0215407

 

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