Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, 1150 West Medical Center Drive, University of Michigan, Ann Arbor 48109-5616, MI, USA.
Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, 1150 West Medical Center Drive, University of Michigan, Ann Arbor 48109-5616, MI, USA.
Hear Res. 2021 May;404:108216. doi: 10.1016/j.heares.2021.108216. Epub 2021 Feb 21.
Mice with chronic cochlear implants can significantly contribute to our understanding of the relationship between cochlear health and implant function because of the availability of molecular tools for controlling conditions in the cochlea and transgenic lines modeling human disease. To date, research in implanted mice has mainly consisted of short-term studies, but since there are large changes in implant function following implant insertion trauma, and subsequent recovery in many cases, longer-term studies are needed to evaluate function and perception under stable conditions. Because frequent anesthetic administration can be especially problematic in mice, a chronic model that can be tested in the awake condition is desirable. Electrically-evoked compound action potentials (ECAPs) recorded with multichannel cochlear implants are useful functional measures because they can be obtained daily without anesthesia. In this study, we assessed changes and stability of ECAPs, electrically-evoked auditory brainstem responses (EABRs), ensemble spontaneous activity (ESA), and impedance data over time after implanting mice with multichannel implants. We then compared these data to histological findings in these implanted cochleae, and compared results from this chronic mouse model to data previously obtained in a well-established chronically-implanted guinea pig model. We determined that mice can be chronically implanted with cochlear implants, and ECAP recordings can be obtained frequently in an awake state for up to at least 42 days after implantation. These recordings can effectively monitor changes or stability in cochlear function over time. ECAP and EABR amplitude-growth functions (AGFs), AGF slopes, ESA levels and impedances in mice with multichannel implants appear similar to those found in guinea pigs with long-term multichannel implants. Animals with better survival of spiral ganglion neurons (SGNs) and inner hair cells (IHCs) have steeper AGF slopes, and larger ESA responses. The time course of post-surgical ear recovery may be quicker in mice and can show different patterns of recovery which seem to be dependent on the degree of insertion trauma and subsequent histological conditions. Histology showed varying degrees of cochlear damage with fibrosis present in all implanted mouse ears and small amounts of new bone in a few ears. Impedance changes over time varied within and across animals and may represent changes over time in multiple variables in the cochlear environment post-implantation. Due to the small size of the mouse, susceptibility to stress, and the higher potential for implant failure, chronic implantation in mice can be challenging, but overall is feasible and useful for cochlear implant research.
慢性耳蜗植入的小鼠可以为我们理解耳蜗健康和植入功能之间的关系提供重要的帮助，因为我们可以使用分子工具来控制耳蜗的条件，并且可以使用转基因模型来模拟人类疾病。迄今为止，植入小鼠的研究主要由短期研究组成，但由于植入创伤后植入功能会发生很大变化，并且在许多情况下会恢复，因此需要进行更长时间的研究，以评估稳定条件下的功能和感知。由于频繁的麻醉管理在小鼠中可能特别成问题，因此需要一种可以在清醒状态下进行测试的慢性模型。使用多通道耳蜗植入物记录的电诱发复合动作电位 (ECAP) 是有用的功能测量指标，因为它们可以每天在不使用麻醉的情况下获得。在这项研究中，我们评估了在植入多通道植入物后，ECAP、电诱发听脑干反应 (EABR)、整体自发活动 (ESA) 和阻抗数据随时间的变化和稳定性。然后，我们将这些数据与这些植入耳蜗的组织学发现进行了比较，并将该慢性小鼠模型的结果与先前在长期植入的豚鼠模型中获得的数据进行了比较。我们确定可以对小鼠进行慢性植入，并且可以在植入后至少 42 天内经常在清醒状态下获得 ECAP 记录。这些记录可以有效地监测随时间推移耳蜗功能的变化或稳定性。多通道植入小鼠的 ECAP 和 EABR 幅度生长函数 (AGF)、AGF 斜率、ESA 水平和阻抗与长期多通道植入的豚鼠相似。具有更多螺旋神经节神经元 (SGN) 和内毛细胞 (IHC) 存活的动物具有更陡峭的 AGF 斜率和更大的 ESA 反应。术后耳朵恢复的时间过程可能在小鼠中更快，并且可以显示出不同的恢复模式，这些模式似乎取决于插入创伤的程度和随后的组织学状况。组织学显示所有植入小鼠耳朵都有不同程度的耳蜗损伤，并且少数耳朵中存在少量新骨。随着时间的推移，阻抗变化在动物内部和之间变化，可能代表植入后耳蜗环境中多个变量随时间的变化。由于小鼠体积小、易受压力影响以及植入物故障的可能性较高，因此慢性植入在小鼠中可能具有挑战性，但总体上是可行的，并且对耳蜗植入研究很有用。
