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.

项目概要 一次爆炸超压，例如由爆炸装置产生的爆炸超压，已成为造成爆炸的一个日益严重的原因。 军人和平民受伤。头晕和身体不平衡是爆炸受害者经常抱怨的问题。 然而，很少有研究探讨爆炸超压对前庭系统的影响，这代表了 在制定有效的前庭疾病预防、诊断和治疗方案方面存在重要的知识差距 爆炸受害者人数不足。为了填补知识空白，该应用的目标是阐明其机制 大鼠模型中爆炸引起的前庭损伤。该应用程序基于我们新开发的爆炸伤害装置 它将冲击波直接传递到老鼠的外耳道中。该模型使我们能够研究以下因素的影响 对前庭系统进行主要冲击，同时避免对其他充气器官造成损害。爆炸引起的 前庭损伤模型经过我们评估前庭毛细胞组织学的初步研究的验证，单个 前庭传入活动和前庭眼反射（VOR）。初步研究结果表明 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 从外周到中央前庭系统的各个层面。初步结果导致我们 假设爆炸暴露会引发 I 型毛细胞介导的通路的退化过程， 前庭功能反映了损伤进展和代偿过程的相互作用。当前的 应用程序将利用新型爆炸损伤模型来识别急性到慢性的形态学、 暴露于爆炸超压引起的前庭缺陷的生理和行为生物标志物 不同强度的波。目标 1 是研究爆炸引起的前庭系统结构损伤。 我们将研究不同的终末器官、前庭毛细胞类型或神经末梢类型是否表现出 不同程度的爆炸暴露敏感性和 6 小时至 12 个月内不同的恢复情况。 我们还将通过分析炎症生物标志物来研究前庭核损伤的进展， 轴突损伤和细胞凋亡。此外，还将构建3D生物力学模型来模拟爆炸 通过内耳传播能量来量化机械效应。目标 2 是采用单一单元记录 评估爆炸暴露后前庭传入神经的损伤进展。自发放电和 将研究来自耳管和耳石的不同传入神经亚群的动态响应。目标 3 是 通过测量旋转和平移 VOR 来评估爆炸引起的前庭损伤进展。两个都 将测量稳态和瞬时 VOR 以评估前庭损伤进展的综合结果 和代偿过程，并确定诊断爆炸诱发前庭的最佳 VOR 范式 受伤。该研究的结果将阐明爆炸引起的前庭缺陷的机制 为早期诊断和干预目标提供重要信息。