Mechanisms of Blast-Induced Vestibular Injury

项目摘要 一次爆炸超压，如爆炸装置产生的超压，已成为越来越多的原因， 军人和平民的伤亡。头晕和失衡是爆炸受害者的常见症状。 然而，很少有研究涉及冲击波超压对前庭系统的影响， 在制定有效的预防、诊断和治疗前庭功能障碍的方案方面存在重要的知识差距 在爆炸受害者中的缺陷。为了填补知识空白，应用程序的目标是阐明 冲击波诱发前庭损伤大鼠模型。该应用程序是建立在我们新开发的爆炸伤设备 将冲击波直接传递到老鼠的外耳道。这个模型使我们能够研究 主要冲击波作用于前庭系统，同时避免损伤其他充气器官。爆炸引起的 前庭损伤模型通过我们评估前庭毛细胞组织学、单个 前庭传入活动和前庭眼反射（VOR）。初步研究的结果表明， 冲击波引起的前庭损伤本质上是复杂的，包括急性损伤和进行性损伤 在从外周到中央前庭系统的所有水平。初步结果导致我们的 假设冲击波暴露触发I型毛细胞介导的途径中的退行性过程， 前庭功能反映了损伤进展和代偿过程的相互作用。电流 应用将利用新的冲击伤模型来鉴定急性至慢性形态学， 冲击波超压暴露引起前庭功能障碍的生理和行为生物标志物 具有不同强度的波。目的1是调查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的功能。 在6小时至12个月的时间内，对爆炸的敏感程度不同，恢复情况也不同。 我们还将通过分析炎症的生物标志物来研究前庭核的损伤进展， 轴突损伤和凋亡。此外，还将建立一个三维生物力学模型来模拟爆炸 通过内耳的能量传播来量化机械效应。目标2是采用单单元记录 评估冲击波暴露后前庭传入神经的损伤进展。自发放电和 将研究来自耳道和耳石的传入神经的不同亚群的动态响应。目标3是 通过测量旋转和平移VOR来评估冲击波诱导的前庭损伤进展。两 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，并确定最佳VOR范式用于诊断爆震诱导的前庭 损伤这项研究的结果将阐明爆炸引起的前庭功能障碍的机制， 为早期诊断和干预目标提供必要信息。

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.