Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, 111 Lock Street, Newark, NJ 07102, USA.
NeuroBehavioral Research Laboratory, VA New Jersey Health Care System, Research and Development (Mailstop 15), 385 Tremont Ave, East Orange, NJ 07018, USA.
Medicina (Kaunas). 2023 Sep 18;59(9):1683. doi: 10.3390/medicina59091683.
: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. : After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. : We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. : In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.
流行病学数据表明,爆炸暴露是最近军事行动中导致军人(SM)轻度创伤性脑损伤(mTBI)最常见的发病率。爆炸引起的耳鸣是退伍军人经常报告的合并症,尽管它的患病率很高,但它也是最不被理解的疾病之一。爆炸引起的耳鸣通常与直接的结构损伤有关,导致听觉系统的传导性和感觉神经性损伤。耳鸣也被认为是由异常神经元活动和神经可塑性的时间变化引起的。临床上,观察到耳鸣常伴有睡眠中断和焦虑增加。在这项研究中,我们阐明了暴露于冲击波和脉冲噪声引起的感觉神经性损伤的一些机制方面。通过采用双耳均受保护的动物模型,最大限度地减少了孤立的传导性听觉损伤假说。
在暴露后,通过听觉惊吓反应(ASR)评估动物的听力电路状态,以区分听力损失和耳鸣。我们还将爆炸引起的耳鸣与成熟的水杨酸钠诱导的耳鸣模型进行了比较,作为阳性对照。听觉脑干反应(ABR)评估感觉神经性听觉系统的状态,该测试有助于检查耳蜗和下丘之间的神经元回路。然后,我们进一步评估了爆炸暴露后兴奋性和抑制性神经递质受体和神经元突触在听觉皮层(AC)损伤中的作用。
我们观察到暴露于爆炸冲击波的动物的 ABR 阈值持续升高,而仅在急性时间点观察到仅受脉冲噪声组的 ABR 阈值短暂变化。这些变化与带突触的表达增加一致,这表明存在神经炎症和细胞能量代谢紊乱。还发现耳鸣的发作伴随着焦虑、抑郁样症状和睡眠模式的改变。通过比较冲击波暴露和脉冲噪声暴露的影响,我们发现冲击波对耳鸣诱导和感觉神经性损伤的影响比脉冲噪声更显著。
在这项研究中,我们系统地研究了爆炸损伤后听觉系统的结构和功能变化,为爆炸诱导的耳鸣的病理生理学提供了更深入的了解。