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

项目摘要 包括儿童在内的50多万患者受益于这项卓越的技术， 人工耳蜗（CI）是一项突破。越来越多的患者有一定程度的残留 听力在植入时，并可以受益于双峰电声装置。残存毛细胞 活动，因此，一个功能性的Corti器官和神经基质最近与语言联系在一起 感知结果。然而，植入过程中的创伤会导致炎症和氧化应激， 加重残余听力损失。成功地将治疗干预措施转化为限制 伤害还没有达到。目前的工作将设计和实现本地化， 治疗性低温用于保护CI后的毛细胞和神经基质。具体目标是 受初步和已发表的数据的激励，这些数据表明，局部的轻度低温传递到耳蜗 是高效和安全的，保护毛细胞和突触组件，保护完整的 耳蜗血-迷路屏障和植入后长期保留残余听力。具体目标1将 测试冷却应用于耳蜗时的安全性和有效性，并制定最佳方案， 长期功能和生理结果。在具体目标2中，使用分子生物学和 免疫组织化学技术，我们将确定低温下的神经保护机制。 结合临床前结果和特定目标3中的人尸体颞骨研究，我们将开发 一种用于人类应用的装置和系统。该系统将能够提供优化的低温治疗 用于植入后的残留结构和功能保护。确保敏感毛细胞的存活， 耳蜗中的神经结构可能导致改善的言语感知结果， 患者受益于未来的技术和/或治疗。该项目的成果可以进一步 扩展到其他内耳相关的创伤，如耳毒性，或噪音和爆炸引起的创伤。

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.