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）：在过去十年中，最令人兴奋的进展之一是开发了在可能导致毛细胞损失的压力条件下保护听力的疗法。然而，目前的治疗方法侧重于保护感觉细胞，最近的结果（Kujawa和Liberman，2006，2009）表明，内毛细胞（MHC）和听神经（AN）之间的连接也可能存在永久性丧失的风险。我们提出的研究检查了在选择用于高临床相关性的两种应力期间IHC-AN连接的损失：噪声诱导的听力损失和在具有剩余听力的耳朵中植入假体，然后测试抗氧化剂（AO）疗法用于保护/恢复的功效，并最终确定在AO疗法中添加抗兴奋毒性疗法是否会改善IHC-AN连接和听力的保护/恢复。目的1-检验以下假设：中等噪声导致许多毛细胞的永久性丧失，也会导致剩余IHC上许多IHC-AN连接的永久性丧失，以及随后的听觉神经元（SGN）丧失。目的2-检验假设（2a）有效减少噪声诱导的毛细胞损失的AO治疗在减少IHC-AN连接损失方面效果较差，以及（2b）添加特异性抗兴奋性毒性治疗将改善IHC-AN连接的保留、SGN的长期存活和听力。目的3 -检验以下假设：将假体插入听力耳的创伤将导致IHC-AN连接丧失，包括毛细胞未丧失的区域。目的4 -检验假设（4a），即增加AO治疗将比IHC-AN连接更有效地保护毛细胞免受假体插入创伤，以及（4 b）在AO治疗中增加特异性抗兴奋毒性治疗将改善IHC-AN连接的保护。目的5 -检验以下假设：减少IHC-AN连接和SGN的丢失将改善听觉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留听力的治疗目标，不仅对治疗正在测试的两种情况（噪音引起的听力损失和将人工耳蜗植入到具有剩余听力的耳朵中）具有高度影响，而且对其他内耳病变（从耳毒性到前庭疾病）的最佳治疗实践具有高度相关性。如果成功，一种新的治疗模式可以直接转化为临床试验，使全球数百万人受益。