Hearing Preservation for Noise or Cochlear Implantation: Mechanisms & Treatments

噪音或人工耳蜗植入的听力保护：机制

• 批准号: 8402850
• 负责人: RICHARD A ALTSCHULER
• 金额: $ 50.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8402850
• 关键词: Acoustic Nerve; Acoustic Trauma; Acoustics; Action Potentials; Animal Model; Animals; Antioxidants; Apoptosis; Apoptotic; Auditory; Auricular prosthesis; Biological Preservation; Cavia; Cell Death Signaling Process; Cell Survival; Cells; Clinical Trials; Cochlear Implants; Cochlear implant procedure; Disease; Ear; Electrodes; Evoked Potentials, Auditory, Brain Stem; Growth; Hair Cells; Hearing; Hybrids; Implant; Individual; Inner Hair Cells; Labyrinth; Lead; Memantine; Metric; Neurons; Noise; Noise-Induced Hearing Loss; Pathology; Performance; Peripheral; Process; Prosthesis; Psychophysics; Recovery; Risk; Sensory; Stress; Synapses; Testing; Translating; Trauma; antioxidant therapy; clinically relevant; ebselen; efficacy testing; excitotoxicity; improved; neuronal cell body; ototoxicity; public health relevance; response; therapy development

DESCRIPTION (provided by applicant): One of the most exciting advances in the last decade has been the development of therapies to preserve hearing under conditions of stress that can otherwise cause hair cell loss. Current therapies, however, focus on preservation of sensory cells and recent results (Kujawa and Liberman, 2006, 2009) indicate that the connections between inner hair cells (IHC) and auditory nerve (AN) may also be at risk for permanent loss. Our proposed studies examine loss of IHC-AN connections during two stresses chosen for high clinical relevance: Noise Induced Hearing Loss and Prostheses Insertion in Ears with Remaining Hearing, then test the efficacy of anti-oxidant (AO) therapy for protection / recovery and finally determine if adding anti- excitotoxicity therapy to the AO therapy will improve protection / recovery of IHC-AN connections and hearing. Aim 1-Test the hypothesis that a moderate noise causing permanent loss of many hair cells will also produce a permanent loss of many IHC-AN connections on remaining IHCs and later loss of auditory neurons (SGN). Aim 2- Test the hypothesis (2a) that AO treatments that effectively reduce noise-induced hair cell loss will be less effective in reducing the loss of IHC-AN connections and (2b) that adding a specific anti-excitotoxicity therapy will improve preservation of IHC-AN connections, long term survival of SGN and hearing. Aim 3 - Test the hypothesis that trauma from insertion of a prostheses into a hearing ear will induce loss of IHC-AN connections, including in regions where hair cells are not lost. Aim 4 - Test the hypothesis (4a) that adding AO treatment will be more effective in preserving hair cells than IHC-AN connections from the trauma of prostheses insertion and (4b) addition of specific anti-excitotoxicity therapy to the AO therapy will improve the preservation of IHC-AN connections. Aim 5 - Test the hypothesis that reducing loss of IHC-AN connections and SGN will improve acoustic hearing and spatial and temporal acuity of psychophysical responses to cochlear implant stimulation. Results of the proposed studies will redefine and broaden treatment targets for preserving hearing with high impact not only toward treating the two conditions being tested, noise-induced hearing loss and implantation of cochlear prostheses into ears with remaining hearing, but with high relevance towards best treatment practices for other inner ear pathologies ranging from ototoxicity to vestibular disorders. If successful, a new treatment paradigm can be directly translated to clinical trials and benefit millions of individuals worldwide.

描述（由申请人提供）：过去十年中最令人兴奋的进步之一是开发在压力条件下保存听力的疗法，否则会导致毛细胞损失。然而，目前的疗法集中于保存感觉细胞和最新结果（Kujawa and Liberman，2006，2009）表明，内毛细胞（IHC）和听觉神经（AN）之间的连接也可能有永久损失的风险。 Our proposed studies examine loss of IHC-AN connections during two stresses chosen for high clinical relevance: Noise Induced Hearing Loss and Prostheses Insertion in Ears with Remaining Hearing, then test the efficacy of anti-oxidant (AO) therapy for protection / recovery and finally determine if adding anti- excitotoxicity therapy to the AO therapy will improve protection / recovery of IHC-AN connections and hearing.目标1检验的假设是，导致许多毛细胞永久损失的中等噪声也将在剩余的IHC和后来的听觉神经元（SGN）丧失的许多IHC AN连接中永久丧失。目标2-检验假设（2a），有效减少噪声诱导的毛细胞损失的AO处理在减少IHC-AN连接的丧失方面的有效性较小，并且（2B）（2B）添加特定的抗脱毒性疗法将改善对IHC-AN的维护，从而可以改善IHC-AN连接，SGN和听力的长期存活。 AIM 3-检验以下假设：从插入假体插入听力耳朵的创伤将导致IHC AN连接的丧失，包括在毛细胞不会丢失的区域。 AIM 4-检验假设（4A），即与IHC-A-a插入的创伤相比，添加AO治疗将在保存毛细胞方面更有效，并且（4B）（4B）在AO治疗中添加特定的抗脱毒性疗法将改善IHC-AN连接的保存。 AIM 5-检验以下假设：减少IHC AN连接和SGN的丧失将改善对耳蜗植入物刺激的心理物理反应的声学听力以及空间和时间的敏锐度。拟议的研究的结果将重新定义并扩大治疗目标，以保持听力，不仅对治疗的两种情况，噪声引起的听力损失以及将耳蜗假体植入到耳朵中，并保持听力较高，而且对其他内部耳朵的最佳治疗方法具有很高的相关性，这些病理因其他内部的病理而言，从眼毒性毒性差异很高。如果成功，可以将新的治疗范式直接转化为临床试验，并受益于全球数百万个人。