Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Stadtfelddamm 34, 30625, Hannover, Germany.
Cluster of Excellence "Hearing4all" of the German Research Foundation, Oldenburg, Germany.
Neurotox Res. 2019 Jul;36(1):204-216. doi: 10.1007/s12640-019-00017-x. Epub 2019 Mar 7.
Patients scheduled for cochlear implantation often retain residual hearing in the low frequencies. Unfortunately, some patients lose their residual hearing following implantation and the reasons for this are not well understood. Evidence suggests that electrotoxicity could be one of the factors responsible for this late adverse effect. Therefore, the aim of this study was to investigate the survival of spiral ganglion neurons (SGN) subjected to in vitro electrical stimulation (ES). A stimulation setup was developed to provide defined electrical fields at given points of the chamber. SGN isolated from Sprague Dawley rats (P3-4) were dissociated and cultured in the chamber for 24 h prior to biphasic, pulsed electrical field exposure for another 24 h. The current varied in the range of 0 to 2 mA and the pulse width from 10 to 400 μs. Neurite growth and survival were evaluated with respect to the charge density at the position of the cells. Non-exposed SGN cultures served as control. Charge densities below 2.2 μC·cm·phase appeared to have no effect on SGN survival and neurite outgrowth. Charge densities above 4.9 μC·cm·phase were detrimental to almost all cells in culture. After fitting results to a sigmoidal dose response curve, a LD of 2.9 μC·cm·phase was calculated. This screening regarding survival and outgrowth of SGN provides parameters that could be used to further investigate the effect of ES on SGN and to develop possible protection strategies, which could potentially rescue residual hearing in the implanted patients.
计划接受人工耳蜗植入的患者通常在低频范围内保留残余听力。不幸的是，一些患者在植入后丧失了残余听力，其原因尚不清楚。有证据表明，电毒性可能是导致这种迟发性不良反应的因素之一。因此，本研究旨在研究体外电刺激（ES）下螺旋神经节神经元（SGN）的存活情况。开发了一种刺激装置，以在腔室的给定点提供定义的电场。将从 Sprague Dawley 大鼠（P3-4）中分离出的 SGN 进行解离，并在腔室中培养 24 小时，然后再进行双相、脉冲电场暴露 24 小时。电流范围为 0 至 2 mA，脉冲宽度为 10 至 400 μs。根据细胞位置的电荷密度评估神经突生长和存活情况。未暴露的 SGN 培养物作为对照。细胞位置的电荷密度低于 2.2 μC·cm·相似乎对 SGN 存活和神经突生长没有影响。电荷密度高于 4.9 μC·cm·相对培养物中的几乎所有细胞都有害。将结果拟合到 S 形剂量反应曲线后，计算出 LD 为 2.9 μC·cm·相。这种关于 SGN 存活和生长的筛选提供了可用于进一步研究 ES 对 SGN 影响并开发可能的保护策略的参数，这可能有助于挽救植入患者的残余听力。
