Mechanisms of Blast-Induced Vestibular Injury

爆炸引起的前庭损伤的机制

• 批准号: 10470913
• 负责人: WU ZHOU
• 金额: $ 52.89万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-11 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10470913
• 关键词: 3-Dimensional; Acute; Address; Air; Animal Model; Apoptosis; Area; Auditory; Behavioral; Biological Markers; Blast Injuries; Brain; Brain Stem; Chronic; Complex; Devices; Diagnosis; Disease; Dizziness; Ear; Early Diagnosis; Elements; Exhibits; Explosion; Exposure to; External Ear; External auditory canal; FOS gene; Financial compensation; Frequencies; Functional disorder; Goals; Grant; Hair Cells; Head; Head Movements; Histology; Histopathology; Hour; Inflammation; Injury; Intervention; Knowledge; Labyrinth; Lead; Literature; Long-Evans Rats; Lung; Masks; Measures; Mechanics; Mediating; Microglia; Military Personnel; Modeling; Morphology; Nature; Nerve; Nerve Endings; Neurons; Organ; Outcome; Pathway interactions; Phase; Physiological; Population; Predisposition; Prevention; Process; Rattus; Recovery; Reporting; Rotation; Shock; Signal Transduction; Site; Structure; Subgroup; Symptoms; System; Time; Translations; Tube; Type I Hair Cell; United States National Institutes of Health; Vestibular Hair Cells; Vestibular ganglion; Vestibular nucleus structure; axon injury; biomechanical model; blast exposure; cell injury; cell type; early detection biomarkers; insight; neuroinflammation; novel; otoconia; response; ribbon synapse; service member; terminal redundancy; treatment program; vestibulo-ocular reflex

Project Summary Primary blast overpressure, such as that produced by explosive devices, has become an increasing cause of injury in both military and civilian populations. Dizziness and imbalance are frequent complaints of blast victims. However, few studies addressed the impact of blast overpressure on the vestibular system, representing an important knowledge gap in developing effective prevention, diagnosis and treatment programs of vestibular deficits in blast victims. To fill the knowledge gap, the goal of the application is to elucidate the mechanisms of blast-induced vestibular injuryin a rat model. The application is built upon our newly developed blast injury device that delivers blast waves directly into the external ear canal of rats. This model allows us investigate impact of primary blast on the vestibular system while avoiding damage to other air-filled organs. The blast-induced vestibular injury model was validated by our preliminary studies that assess vestibular hair cell histology, single vestibular afferent activity and vestibulo-ocular reflex(VOR). Results fromthe preliminary studies suggested that blast-induced vestibular injury is complex in nature and involves a combination of acute and progressive injury at all levels spanning from the periphery to the central vestibular system. The preliminary results lead to our hypothesis that blast exposure triggers degenerative processes in the Type I hair cell mediated pathways and the vestibular function reflects interactions of injury progression and compensatory processes. Current application will take advantage of the novel blast injury model to identify acute-to-chronic morphological, physiological and behavioral biomarkers of the vestibular deficits caused by exposure to blast overpressure waves with different intensities. Aim 1 is to investigate blast-induced structural damage to the vestibular system. We will investigate whether different end organs, types of vestibular hair cells or types of nerve endings exhibit different levels of susceptibility to blast exposure and different recovery over a period of 6 hours to 12 months. We will also investigate injury progression in the vestibular nuclei by analyzing biomarkers of inflammation, axonal damage and apoptosis. In addition, a 3D biomechanical model will be constructed to simulate blast energy propagation through the inner ear to quantify mechanical effects. Aim 2 is to employ single unit recording to assess injury progression in vestibular afferents following blast exposure. Spontaneous discharge and dynamic responses of different subgroups of afferents from the canals and otoliths will be studied. Aim 3 is to assess blast-induced vestibular injury progression by measuring the rotational and translational VORs. Both steady state and transient VORs will be measured to assess integrative outcomes of vestibularinjury progression and compensatory processes and identify the optimal VOR paradigms for diagnosis of blast-induced vestibular injury. Results from the study will elucidate the mechanisms underlying blast-induced vestibular deficits and provide essential information for early diagnosis and targets for intervention.

项目摘要 主要的爆炸过压，例如由爆炸装置产生的过压，已成为越来越多的原因 军事和平民的伤害。头晕和失衡是爆炸受害者的经常抱怨。 但是，很少有研究解决了爆炸过压对前庭系统的影响，代表 重要的知识差距在开发前庭有效预防，诊断和治疗计划中 爆炸受害者的缺陷。为了填补知识差距，应用程序的目的是阐明 爆炸诱导的前庭损伤A大鼠模型。该应用是建立在我们新开发的爆炸损伤装置上的 那将爆炸波直接传递到大鼠外耳管中。该模型使我们研究了 前庭系统上的主要爆炸，同时避免损坏其他充气器官。爆炸引起的 我们的初步研究对前庭损伤模型进行了验证，该研究评估了前庭毛细胞组织学，单个 前庭传入活动和前庭 - 眼反射（VOR）。初步研究的结果表明 爆炸引起的前庭损伤本质上很复杂，涉及急性和进行性损伤的结合 从周围到中央前庭系统的各个级别。初步结果导致我们 假设爆炸暴露会触发I型毛细胞介导的途径和 前庭功能反映了损伤进展和补偿过程的相互作用。当前的 应用将利用新型的爆炸损伤模型来识别急性到智的形态， 前庭缺陷的生理和行为生物标志物导致暴露于爆炸过压 强度不同的波。目的1是研究爆炸引起的对前庭系统的结构损害。 我们将调查不同的端器官，前庭毛细胞类型或神经末端的类型是否表现出来 在6小时至12个月的时间内，不同程度的爆炸暴露和不同恢复的易感性。 我们还将通过分析炎症的生物标志物，研究前庭核的损伤进展 轴突损伤和凋亡。此外，将构建一个3D生物力学模型以模拟爆炸 通过内耳传播能量以量化机械效应。 AIM 2是使用单个单元记录 评估爆炸暴露后前庭传入的损伤进展。自发放电和 将研究从运河和耳石的不同亚组的动态响应。目标3是 通过测量旋转和翻译VOR来评估爆炸诱导的前庭损伤进展。两个都 将测量稳态和瞬态VOR，以评估前庭抑制进展的综合结果 和补偿过程，并确定诊断爆炸诱导的前庭的最佳范式 受伤。该研究的结果将阐明爆炸诱导的前庭缺陷和 提供早期诊断的基本信息和干预目标。