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: 8210832
• 负责人: RICHARD A ALTSCHULER
• 金额: $ 55.42万
• 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/8210832
• 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; Psychophysiology; 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. PUBLIC HEALTH RELEVANCE: Our proposed studies are to develop and test better treatments to preserve hearing during two traumatic stresses to the ear, chosen for high clinical relevance: Noise Induced Hearing Loss and Prostheses Insertion in Ears with Remaining Hearing.

描述（由申请人提供）：过去十年中最令人兴奋的进展之一是开发了在压力条件下保持听力的疗法，否则会导致毛细胞损失。然而，目前的疗法侧重于感觉细胞的保存，最近的结果（Kujawa 和 Liberman，2006，2009）表明内毛细胞（IHC）和听觉神经（AN）之间的连接也可能面临永久丧失的风险。我们提出的研究检查了在选择具有高度临床相关性的两种压力期间 IHC-AN 连接的丧失：噪声引起的听力损失和在剩余听力的耳朵中插入假体，然后测试抗氧化 (AO) 疗法的保护/恢复效果，最后确定在 AO 治疗中添加抗兴奋性毒性治疗是否会改善 IHC-AN 连接和听力的保护/恢复。目标 1 - 测试以下假设：导致许多毛细胞永久丧失的中等噪音也会导致剩余 IHC 上的许多 IHC-AN 连接永久丧失，并随后导致听觉神经元 (SGN) 丧失。目标 2- 检验假设 (2a)，有效减少噪音引起的毛细胞损失的 AO 治疗在减少 IHC-AN 连接损失方面效果较差，(2b) 添加特定的抗兴奋性毒性治疗将改善毛细胞的保存IHC-AN 连接、SGN 和听力的长期存活。目标 3 - 测试以下假设：将假体插入听力耳朵造成的创伤会导致 IHC-AN 连接丢失，包括毛细胞未丢失的区域。目标 4 - 检验假设 (4a)，即添加 AO 治疗比 IHC-AN 连接更能有效地保护毛细胞免受假体插入创伤的影响，并且 (4b) 在 AO 治疗中添加特定的抗兴奋性毒性治疗将改善毛细胞的毛细胞保留 IHC-AN 连接。目标 5 - 测试以下假设：减少 IHC-AN 连接和 SGN 的丢失将改善声学听力以及对人工耳蜗刺激的心理物理反应的空间和时间敏锐度。拟议研究的结果将重新定义和扩大保护听力的治疗目标，不仅对治疗两种正在测试的疾病（噪音引起的听力损失和在保留听力的情况下将人工耳蜗植入耳朵）产生重大影响，而且与最佳治疗高度相关从耳毒性到前庭疾病等其他内耳疾病的实践。如果成功，新的治疗模式可以直接转化为临床试验，并使全世界数百万人受益。 公共健康相关性：我们提出的研究旨在开发和测试更好的治疗方法，以在耳朵受到两种创伤性压力时保持听力，选择这些方法是为了高度临床相关性：噪声引起的听力损失和在剩余听力的耳朵中植入假体。