Effect of Inner Hair Cell Loss and Afferent Damage on Functional Hearing

内毛细胞损失和传入损伤对功能性听力的影响

• 批准号: 9238370
• 负责人: Edward Lobarinas
• 金额: $ 33.94万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-07 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9238370
• 关键词: Acoustic Nerve; Action Potentials; Acute; Animal Experiments; Animal Model; Animals; Applications Grants; Audiometry; Auditory; Auditory Brainstem Responses; Auditory Evoked Potentials; Behavioral; Bilateral; Carboplatin; Chinchilla (genus); Chronic; Data; Diagnosis; Discrimination; Dose; Early Diagnosis; Early Intervention; Evoked Potentials; Exposure to; Frequencies; Goals; Growth; Health; Hearing; Human; Hyperacusis; Individual; Inner Hair Cells; Label; Labyrinth; Lesion; Loudness; Masks; Measures; Modeling; Monitor; Nerve Fibers; Noise; Noise-Induced Hearing Loss; Occupational Noise; Output; Pathology; Pattern; Phase; Physiological; Presbycusis; Rehabilitation therapy; Risk Factors; Site; Speech; Synapses; Testing; Tinnitus; Work; behavior measurement; density; early onset; hazard; hearing impairment; interest; ototoxicity; programs; relating to nervous system; response

ABSTRACT Audiometry, or threshold testing at frequencies essential for speech understanding, is the most common and universally accepted metric for hearing health. However, it is becoming clear from animal studies that there can be significant inner ear damage that is undetected by threshold measures and among hearing impaired individuals there can be substantial variability in functional metrics of hearing such as hearing in noise even across individuals with similar thresholds and no evidence of retrocochlear pathology. These findings have generated tremendous interest in “hidden hearing loss” characterized by inner ear damage that is undetected by threshold measures. There is now speculation that loss of afferent synapses may underlie hearing-in-noise deficits, hyperacusis, and tinnitus. However, what is the evidence for functional deficits and where do these deficits begin? Surprisingly, there is no current evidence of any significant functional deficits associated with synaptopathy in animals and there is no compelling evidence in humans. Thus, it is essential to determine the critical boundaries for when functional deficits associated with hidden hearing loss begin. Establishing the relationship between specific patterns of cochlear damage such as loss of inner hair cells (IHC) or synapses and the corresponding functional deficits undetected by thresholds are critical in understanding risk factors, early detection, and intervention for early onset or undetected hearing loss. The overall aims of this proposal is to evaluate functional hearing impairment in an animal model with degradation of afferent synapses using noise-exposure or selective ototoxic loss of inner hair cells in the absence of corresponding threshold elevations. Specifically, what is the effect of this “hidden” but significant cochlear pathology on hearing-in-noise, intensity discrimination, forward masking, tinnitus and physiological correlates of functional hearing? When do these deficits begin? When completed, this work will explicitly define the functional deficits encompassed within “hidden hearing losses” induced by noise exposure or carboplatin. These data will provide the evidence urgently needed to guide potential changes to auditory monitoring plans recommended as best practice in hearing conservation programs, enhance site of lesion diagnosis, and reveal hidden functional deficit targets for rehabilitative purposes.

摘要 听力测定，或在对言语理解至关重要的频率上的阈值测试，是最常见的， 普遍接受的听力健康指标。然而，从动物研究中可以清楚地看出， 严重的内耳损伤，无法通过阈值测量检测到，并且听力受损 在个体中，听力的功能度量（例如，在噪声中的听力，甚至 在具有相似阈值且没有耳蜗后病变证据的个体之间。这些发现 引起了人们对“隐性听力损失”的极大兴趣， 门槛措施。现在有人猜测，传入突触的丧失可能是噪音中听力的基础 听力缺陷、听觉过敏和耳鸣。然而，什么是功能缺陷的证据，这些证据在哪里？ 赤字开始？令人惊讶的是，目前还没有证据表明任何重大的功能缺陷与 在动物中存在突触病，并且在人类中没有令人信服的证据。因此，必须确定 与隐性听力损失相关的功能缺陷何时开始开始的临界边界。建立 耳蜗损伤的特定模式之间的关系，如内毛细胞（IHC）或突触的损失 并且阈值未检测到的相应功能缺陷对于理解风险因素至关重要， 早期发现和干预早发性或未发现的听力损失。 本提案的总体目标是在动物模型中评价功能性听力损伤， 使用噪声暴露或内毛细胞的选择性耳毒性损失的传入突触的降解 没有相应的门槛。具体来说，这种“隐蔽”却意义重大的效果究竟如何 耳蜗病理学对噪声中听力、强度辨别、前掩蔽、耳鸣和生理 功能性听力的相关因素这些赤字开始是什么时候？完成后，这项工作将明确定义 功能缺陷包括在由噪声暴露或卡铂引起的“隐性听力损失”中。 这些数据将提供迫切需要的证据来指导听觉监测计划的潜在变化 建议作为听力保护计划的最佳实践，增强病变部位诊断，并揭示 隐藏的功能缺陷目标，用于康复目的。