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 无论是军人还是平民都受到了伤害。头晕和身体不平衡是爆炸受害者经常抱怨的问题。 然而，很少有研究涉及爆炸超压对前庭系统的影响，这表明 制定有效的前庭疾病预防、诊断和治疗方案方面的重要知识差距 爆炸受害者的缺陷。为了填补知识空白，应用程序的目标是阐明 冲击波致大鼠前庭损伤模型。该应用程序建立在我们新开发的爆炸伤设备基础上 这会将冲击波直接发射到大鼠的外耳道。此模型使我们能够调查 对前庭系统进行主要冲击波，同时避免对其他充满空气的器官造成损害。爆炸引发的 前庭损伤模型通过我们评估前庭毛细胞组织学的初步研究得到验证， 前庭传入活动和前庭-眼反射(VOR)。初步研究的结果表明 冲击性前庭损伤性质复杂，既有急性损伤，也有进行性损伤。 从外周到中央前庭系统的所有水平。初步结果导致了我们的 假设冲击波暴露触发I型毛细胞介导的通路和 前庭功能反映了损伤进展和代偿过程的相互作用。当前 应用程序将利用新的冲击伤模型来识别从急性到慢性的形态， 冲击波超压暴露所致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研究冲击波对前庭系统的结构性损伤。 我们将研究不同的终末器官、类型的前庭毛细胞或类型的神经末梢 6小时至12个月期间对爆炸暴露的不同敏感性和不同的恢复情况。 我们还将通过分析炎症的生物标志物来研究前庭核团的损伤进展， 轴突损伤和细胞凋亡。此外，还将构建三维生物力学模型来模拟爆炸 能量通过内耳传播，以量化机械效应。目标2是使用单一单元记录 目的：评估爆炸暴露后前庭传入神经的损伤进展。自发放电和 我们将研究不同亚群的神经管和耳石传入的动态反应。目标3是 通过测量旋转和平移的VORS来评估冲击波诱导的前庭损伤进展。两者都有 将测量稳态和瞬时VORS以评估前庭损伤进展的综合结果 和代偿过程，并确定诊断冲击波诱发前庭的最佳VOR范例 受伤。这项研究的结果将阐明冲击波诱导的前庭功能障碍和 为早期诊断和干预目标提供必要的信息。

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.