Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Hear Res. 2021 Aug;407:108292. doi: 10.1016/j.heares.2021.108292. Epub 2021 Jun 7.
The use of explosive devices in war and terrorism has increased exposure to concussive blasts among both military personnel and civilians, which can cause permanent hearing and balance deficits that adversely affect survivors' quality of life. Significant knowledge gaps on the underlying etiology of blast-induced hearing loss and balance disorders remain, especially with regard to the effect of blast exposure on the vestibular system, the impact of multiple blast exposures, and long-term recovery. To address this, we investigated the effects of blast exposure on the inner ear using a mouse model in conjunction with a high-fidelity blast simulator. Anesthetized animals were subjected to single or triple blast exposures, and physiological measurements and tissue were collected over the course of recovery for up to 180 days. Auditory brainstem responses (ABRs) indicated significantly elevated thresholds across multiple frequencies. Limited recovery was observed at low frequencies in single-blasted mice. Distortion Product Otoacoustic Emissions (DPOAEs) were initially absent in all blast-exposed mice, but low-amplitude DPOAEs could be detected at low frequencies in some single-blast mice by 30 days post-blast, and in some triple-blast mice at 180 days post-blast. All blast-exposed mice showed signs of Tympanic Membrane (TM) rupture immediately following exposure and loss of outer hair cells (OHCs) in the basal cochlear turn. In contrast, the number of Inner Hair Cells (IHCs) and spiral ganglion neurons was unchanged following blast-exposure. A significant reduction in IHC pre-synaptic puncta was observed in the upper turns of blast-exposed cochleae. Finally, we found no significant loss of utricular hair cells or changes in vestibular function as assessed by vestibular evoked potentials. Our results suggest that (1) blast exposure can cause severe, long-term hearing loss which may be partially due to slow TM healing or altered mechanical properties of healed TMs, (2) traumatic levels of sound can still reach the inner ear and cause basal OHC loss despite middle ear dysfunction caused by TM rupture, (3) blast exposure may result in synaptopathy in humans, and (4) balance deficits after blast exposure may be primarily due to traumatic brain injury, rather than damage to the peripheral vestibular system.
爆炸装置在战争和恐怖主义中的使用增加了军事人员和平民遭受冲击爆炸的风险,这可能导致永久性听力和平衡缺陷,对幸存者的生活质量产生不利影响。目前仍存在关于爆炸引起听力损失和平衡障碍的潜在病因的重大知识空白,特别是关于爆炸暴露对前庭系统的影响、多次爆炸暴露的影响以及长期恢复的影响。为了解决这个问题,我们使用结合高保真爆炸模拟器的小鼠模型研究了爆炸暴露对内耳的影响。对麻醉动物进行单次或三次爆炸暴露,在长达 180 天的恢复过程中进行生理测量和组织收集。听觉脑干反应 (ABR) 表明多个频率的阈值显著升高。单次爆炸暴露的小鼠在低频时观察到有限的恢复。所有爆炸暴露的小鼠的畸变产物耳声发射 (DPOAE) 最初均缺失,但在爆炸后 30 天的一些单次爆炸暴露的小鼠中可以检测到低频的低振幅 DPOAE,而在爆炸后 180 天的一些三次爆炸暴露的小鼠中可以检测到高频的 DPOAE。所有爆炸暴露的小鼠在暴露后立即出现鼓膜 (TM) 破裂的迹象,以及基底耳蜗转中毛细胞 (OHC) 的缺失。相比之下,爆炸暴露后毛细胞内 (IHC) 和螺旋神经节神经元的数量没有变化。在爆炸暴露的耳蜗上半部分观察到 IHC 前突触突的显著减少。最后,我们发现,前庭诱发电位评估的前庭功能没有明显的耳石细胞丢失或变化。我们的结果表明:(1)爆炸暴露会导致严重、长期的听力损失,这可能部分是由于 TM 愈合缓慢或愈合后的 TM 机械特性改变所致;(2)尽管 TM 破裂导致中耳功能障碍,但仍有创伤性水平的声音可以到达内耳并导致基底 OHC 缺失;(3)爆炸暴露可能导致人类突触病;(4)爆炸暴露后的平衡缺陷可能主要是由于创伤性脑损伤,而不是外周前庭系统的损伤。