Application of mild therapeutic hypothermia for hearing conservation during cochlear implant surgeries

项目摘要 包括儿童在内的50多万名患者已经从这项非凡的技术中受益 突破性的是人工耳蜗术(CI)。越来越多的患者有一定程度的残留 在植入时的听力，并可受益于双峰电声设备。存活毛细胞 活动，因此，一个功能器官的科尔蒂和神经底物最近被联系到语言 感知结果。然而，植入过程中的创伤会导致炎症和氧化应激，从而 加重残留听力损失。治疗干预措施的成功转化，以限制疾病的病理生理 受伤的情况还没有实现。本工作将设计和实现本地化的、 治疗性低温对脑梗塞后毛细胞和神经基质的保护作用。具体目标是 初步和已发表的数据显示，局部的、轻微的体温过低传递到耳蜗处。 是高效和安全的，保护毛细胞和突触组件，保护 人工耳蜗血-迷路屏障及长期保留残留听力。具体目标1将 测试降温应用于耳蜗术的安全性和有效性，并开发一种改进的最佳方案 长期的功能和生理结果。在特定目标2中使用分子生物学和 免疫组织化学技术我们将确定低温背后的神经保护机制。 结合临床前研究结果和人类身体颞骨研究的具体目标3，我们将开发 一种用于人类应用的设备和系统。该系统将能够提供优化的低温治疗 用于种植后的残留结构和功能保护。确保敏感毛细胞的存活和 耳蜗神经结构可能导致改善言语感知结果，并将使 患者将从未来的技术和/或治疗中受益。这个项目的结果可以进一步 扩展到其他与内耳相关的创伤，如耳毒性，或噪音和冲击波引起的创伤。

Project Summary More than half a million patients, including children, have benefitted from the remarkable technological breakthrough that are cochlear implants (CI). An increasing number of patients have some level of residual hearing at the time of implantation and can benefit from bimodal electro-acoustic devices. Surviving hair cell activity and as a result a functioning organ of Corti and neural substrate has recently been linked to speech perception outcomes. However, trauma during implantation leads to inflammation and oxidative stress that can exacerbate residual hearing loss. Successful translation of therapeutic interventions to limit pathophysiology of the injury have yet to be achieved. The present work will design and implement applications of localized, therapeutic hypothermia for protection of hair cells and neural substrate following CI. The specific aims are motivated by preliminary and published data showing that localized, mild hypothermia delivered to the cochlea is highly effective and safe, protecting hair cells and synaptic components, protecting the integrity of the cochlear blood-labyrinth barrier and preserving residual hearing long-term after implantation. Specific aim 1 will test safety and efficacy of cooling when applied to the cochlea and develop an optimal protocol for improved long-term functional and physiological outcomes. In specific aim 2 using molecular biology and immunohistochemistry techniques we will define the neuroprotective mechanisms underlying hypothermia. Combining the preclinical results with human cadaver temporal bone studies in specific aim 3, we will develop a device and system for human application. The system will enable delivery of optimized hypothermia therapy for residual structure and functional protection post-implant. Ensuring the survival of sensitive hair cells and neural structures in the cochlea are likely to lead to improved speech perception outcomes and will enable patients to benefit from future technologies and/or therapies. The results from this project can be further extended to other inner ear-related trauma such as ototoxicity, or noise- and blast-induced trauma.