Intense Noise Exposure Impacts Performance of Vestibular Dependent Behaviors

摘要 军事人员在现役生涯中暴露在强烈的噪声中，来自武器、爆炸和 军用车辆，如坦克、直升机和其他飞机。暴露在强烈的噪音中会导致听力损失 也可能导致前庭功能障碍。虽然听力损失和耳蜗性突触已经被很好地研究了， 外周性前庭突触病变和前庭功能障碍的研究较少，特征也较差。 此外，与年龄相关的平衡赤字对美国退伍军人来说是一个重大的公共卫生问题。 Agrawal等人。报告说，35%的40岁以上的成年人有姿势不稳定和平衡的证据 功能障碍随着年龄的增长而增加，因此在80岁时，85%的成年人报告有平衡问题。前庭 功能障碍会增加跌倒的可能性；在美国，跌倒是导致心脏功能显著下降的原因 生活质量，和超过50%的意外死亡。尽管姿势不稳的原因很复杂 多因素研究表明，噪声引起的听力损失与前庭有关 人类的功能障碍。噪声暴露作为前庭损失的危险因素有明显和显著的老兵 对健康的影响，但很少有研究(1)提供对生理基础的洞察 为退伍军人提供预防或康复策略的指导 有平衡障碍。拟议中的研究将在老鼠模型中显示，在遇到的水平上的噪音暴露 退伍军人在服兵役和日常生活中会导致前庭功能障碍，包括 前庭反射和前庭信号缺陷会增加跌倒的风险，降低头部稳定性和视力 在运动中的敏锐度。 我们假设强烈的噪声暴露足以减弱前庭神经对线性 加速(由前庭短潜伏期诱发电位(VsEP)评估)也将导致显著 前庭三种依赖行为的功能缺陷：(1)运动时的平衡控制；(2)缺陷 前庭结肠反射功能降低头部稳定性；以及(3)前庭-眼反射功能缺陷 足以降低运动时的视力。 具体目标1.评估暴露在足以消除噪声的强烈噪声中的大鼠的平衡、头部和视觉稳定性 VsEP反应至少28天。我们将利用这个时间窗口来探索时间进程和性质 噪声暴露导致的前庭依赖行为缺陷。具体目标2 A。确定是否或 不同的行为会因单一的噪声暴露而受到损害，这种噪声暴露会导致暂时性的损失和恢复 VsEP反应在28天内。这一目的将确定是否存在功能性前庭影响 噪声暴露后，外周突触和VsEP反应恢复。具体目标2B。测定 这些行为的程度和时间进程受到多重噪声暴露的损害， 最初诱导VsEP反应的暂时性衰减。这一目标将决定前庭的累积 重复性噪声暴露的影响(退伍军人在服役期间通常会经历这种情况) 关于康复策略可以针对的潜在的外周和中枢康复机制。

Abstract Military personnel are exposed to intense noise during their active duty careers from weaponry, explosions and military vehicles such as tanks, helicopters and other aircraft. Exposure to intense noise causes hearing loss and may also cause vestibular dysfunction. Although hearing loss and cochlear synaptopathy are well studied, peripheral vestibular synaptopathy and vestibular dysfunction are less often studied and poorly characterized. Furthermore, age related balance deficits are a significant public health problem for veterans in the United States. Agrawal et al. reported that 35% of adults older than 40 had evidence of postural instability and balance dysfunction increased with age so that by 80 years, 85% of adults reported balance problems. Vestibular dysfunction can increase the likelihood of falling; in the US falls are responsible for significant decrements in quality of life, and more than 50% of accidental deaths. Although the causes of postural instability are complex and multifactorial, several studies demonstrate a linkage between noise induced hearing loss and vestibular dysfunction in humans. Noise exposure as a risk factor for vestibular loss has obvious and significant veteran health implications, but there are few, if any studies that (1) provide insights into the physiology that underlies noise-induced vestibular loss and (2) provide guidance for preventative or rehabilitative strategies for veterans with balance disorders. The proposed studies will show in a rat model, that noise exposure at levels encountered by veterans during their military service and during daily life can cause vestibular dysfunction that includes deficits in vestibular reflexes and vestibular signaling that increase fall risk and reduce head stability and visual acuity during movement. We hypothesize that intense noise exposure sufficient to attenuate vestibular nerve responses to linear acceleration (as assessed by the Vestibular short latency Evoked Potential (VsEP) will also cause significant functional deficits in three vestibular dependent behaviors, (1) control of balance during locomotion; (2) deficits in vestibulocollic reflex function that reduce head stability; and (3) deficits in vestibulo-ocular reflex function sufficient to reduce visual acuity during locomotion. Specific Aim 1. Assess balance, head, and visual stability in rats exposed to intense noise sufficient to abolish VsEP responses for at least 28 days. We will use this time window to probe the time course and nature of deficits in vestibular dependent behaviors caused by noise exposure. Specific Aim 2A. Determine whether or not the same behaviors are impaired by a single noise exposure that induces temporary loss and recovery of VsEP responses within 28 days. This Aim will determine if there is a functional vestibular impact from a single noise exposure after which peripheral synapses and VsEP responses recover. Specific Aim 2B. Determine the extent to which and the time course over these behaviors are impaired by multiple noise exposures that initially induce temporary attenuations of VsEP responses. This Aim will determine the cumulative vestibular impact of repetitive noise exposures (as would typically be experienced by Veterans during their service years) on potential peripheral and central recovery mechanisms that can be targeted by rehabilitative strategies.