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

亚低温治疗在人工耳蜗植入手术中听力保护中的应用

• 批准号: 10327695
• 负责人: Suhrud M. Rajguru
• 金额: $ 40.46万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-11 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10327695
• 关键词: Acoustic Stimulation; Acoustics; Acute; Address; Affect; Age; Apoptosis; Auditory; Auditory Brainstem Responses; Auditory area; Biological; Blood; Blood Vessels; Cadaver; Caspase; Cell Count; Cell Death; Cell Survival; Cell physiology; Child; Cisplatin; Clinical; Clinical Protocols; Cochlea; Cochlear Implants; Cochlear implant procedure; Custom; Data; Development; Devices; Electric Stimulation; Elements; Eligibility Determination; Ensure; Face; Fibrosis; Functional disorder; Future; Gender; Gene Expression; Hair Cells; Head and Neck Surgery; Hearing; Histologic; Homeostasis; Human; Hypoxia; Immunohistochemistry; Implant; Inflammation; Inflammatory; Injury; Intervention; Knowledge; Labyrinth; Lead; Link; Maintenance; Measurement; Measures; Mechanics; Mediating; Modeling; Molecular; Molecular Biology; Neurons; Noise; Operating Rooms; Operative Surgical Procedures; Organ of Corti; Outcome; Oxidative Stress; Pathway interactions; Patients; Pharmacologic Substance; Physiologic Ossification; Physiological; Pre-Clinical Model; Procedures; Protocols documentation; Publishing; Reaction; Regimen; Reperfusion Injury; Research; Residual state; Reverse Transcriptase Polymerase Chain Reaction; Rewarming; Safety; Sensorineural Hearing Loss; Sensory Hair; Signal Pathway; Speech Perception; Stria Vascularis; Structure; Synapses; System; Techniques; Technology; Temperature; Temporal bone structure; Testing; Therapeutic; Therapeutic Intervention; Time; Translations; Trauma; Tympanostomy; Work; base; clinical application; clinical translation; cytokine; design; effective therapy; experimental study; functional outcomes; hearing impairment; hearing preservation; implantation; improved; industry partner; ischemic injury; natural hypothermia; neuroprotection; next generation; otoacoustic emission; ototoxicity; pre-clinical; preservation; protective effect; public health relevance; relating to nervous system; round window; safety testing; spiral ganglion; standard of care; technological innovation; therapeutically effective; transcriptome sequencing

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.