The Effect of Noise Exposure on the Vestibular System

噪音暴露对前庭系统的影响

• 批准号: 9079646
• 负责人: Faith Wurm Akin
• 金额: --
• 依托单位: JAMES H QUILLEN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9079646
• 关键词: 3-nitrotyrosine; 4 hydroxynonenal; Address; Animal Model; Animals; Antibodies; Area; Auditory; Cells; Cervical; Clinical; Clinical Protocols; Cochlea; Control Groups; Development; Diagnosis; Dizziness; Epithelium; Equilibrium; Evaluation; Exposure to; Fire - disasters; Free Radical Formation; Frequencies; Functional disorder; Goals; Head; Hearing; Human; Individual; Investigation; Knowledge; Magnetic Resonance Imaging; Manganese; Maps; Military Personnel; Mission; Modeling; Molecular; Neuraxis; Neurons; Noise; Noise-Induced Hearing Loss; Organ; Outer Hair Cells; Pathway interactions; Patient Care; Peripheral; Quality of life; Rattus; Saccule and Utricle; Safety; Semicircular canal structure; Sensory; Sensory Receptors; Services; Symptoms; System; Test Result; Testing; Therapeutic; Utricle structure; Vertigo; Vestibular Function Tests; Vestibular Hair Cells; Vestibular Nerve; Vestibular loss; Veterans; Work; arm; equilibration disorder; hearing impairment; imaging modality; improved; interest; novel; novel therapeutics; otoconia; prevent; public health relevance; rehabilitation strategy; vestibular pathway

 DESCRIPTION (provided by applicant): Observations in the military have shown that exposure to battlefield-related noise can cause balance disorders characterized by postural instability, dizziness, and vertigo; however, underlying mechanisms are not well understood. One reason for this knowledge gap may be that most previous assessments have been focused on evaluation of horizontal semicircular canal function. Recent animal and human studies, however, provide evidence that noise overstimulation impacts the "sacculus;" the vestibular end-organ closest to cochlea, to a much greater extent than any of the other vestibular sensory receptors (Akdogan et al., 2009; Akin et al., 2012). New developments in the use of cervical and ocular vestibular evoked myogenic potentials combined with video head impulse testing, now allow all five vestibular sensory organs (three semicircular canals and two otolith end organs - utricle and saccule) to be assessed in a comprehensive manner that allows the functional integrity of each to be differentiated. This novel test battery allows assessment in a rapid and non-invasive manner following noise exposure. The underlying hypothesis of the proposed studies is that a noise sufficient to induce hearing loss can also induce dysfunction in the sacculus, often without effects on other vestibular end-organs. This will be tested in Veterans with noise-induced hearing loss and in the rat, with the animal studies able to define and control the noise exposure conditions. The use of parallel human and animal studies provides the ability to correlate specific cellular damage (from animal studies) with the noise-induced dysfunction (found in both the human and animal investigations) as well as to identify underlying molecular mechanisms that could point to therapeutics for treatment. Manganese enhanced magnetic resonance imaging (MEMRI) is a powerful imaging modality used to map and assess whether a central nervous system pathway remains intact following insult and to determine changes in activity following peripheral damage (Pautler, 2004, 2006; Holt et al., 2010; Cacace et al., 2014). We hypothesize that sacculus evoked central vestibular activity will change following noise overstimulation. Specific Aim 1: Test the hypothesis that noise that causes permanent threshold shifts in hearing sensitivity will also cause vestibular dysfunction in the sacculus with less effet in the utricle and semicircular canals in humans and in animals. Specific Aim 2A: Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause loss of vestibular hair cells and calyceal vestibular nerve connections and this loss will primarily be found in the sacculus with less effect in the utricle or semicircular canals. Aim 2B: Test the hypothesis that noise overstimulation that causes increased free radical formation in cochlear sensorineural epithelium will cause a similar increase in the sacculus. Specific Aim 3: Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause changes in neuronal activity within the sacculus-associated central vestibular pathways.

 描述（由申请人提供）： 军方的观察表明，暴露于与战场相关的噪音会导致平衡障碍，其特征是姿势不稳定、头晕和眩晕；然而，其根本机制尚不清楚。造成这种知识差距的原因之一可能是以前的大多数评估都集中在水平半规管功能的评估上。然而，最近的动物和人类研究提供了证据表明噪音过度刺激会影响“球囊”；最接近耳蜗的前庭终末器官，其程度比任何其他前庭感觉受体都要大得多（Akdogan 等人，2009 年；Akin 等人，2012 年）。使用颈部和眼部前庭诱发肌源电位与视频头脉冲测试相结合的新进展，现在允许以全面的方式评估所有五个前庭感觉器官（三个半规管和两个耳石终末器官 - 椭圆囊和球囊），从而区分每个感觉器官的功能完整性。这种新颖的测试电池可以在噪声暴露后以快速、非侵入性的方式进行评估。拟议研究的基本假设是，足以引起听力损失的噪音也会引起球囊功能障碍，通常不会影响其他前庭终末器官。这将在患有噪音引起的听力损失的退伍军人和大鼠中进行测试，动物研究能够定义和控制噪音暴露条件。平行的人类和动物研究的使用提供了将特定细胞损伤（来自动物研究）与噪声引起的功能障碍（在人类和动物研究中发现）相关联的能力，以及确定可能指向治疗方法的潜在分子机制。锰增强磁共振成像 (MEMRI) 是一种强大的成像方式，用于绘制和评估中枢神经系统通路在损伤后是否保持完整，并确定外周损伤后活动的变化（Pautler，2004、2006；Holt 等，2010；Cacace 等，2014）。我们假设球囊诱发的中枢前庭活动将在噪声过度刺激后发生变化。具体目标 1：检验以下假设：导致听力敏感度永久性阈值偏移的噪声也会导致球囊前庭功能障碍，而对人类和动物的椭圆囊和半规管影响较小。具体目标 2A：检验以下假设：导致耳蜗外毛细胞中度损失的噪声也会导致前庭毛细胞和盏前庭神经连接的损失，并且这种损失主要出现在球囊中，对椭圆囊或半规管影响较小。目标 2B：检验以下假设：噪声过度刺激导致耳蜗感音神经上皮中自由基形成增加，也会导致球囊类似增加。具体目标 3：检验以下假设：导致耳蜗外毛细胞中度损失的噪音也会导致球囊相关的中央前庭通路内的神经元活动发生变化。