School of Aerospace and Mechanical Engineering, University of Oklahoma, 865 Asp Avenue, Room 200, Norman, OK, 73019, USA.
J Assoc Res Otolaryngol. 2022 Oct;23(5):603-616. doi: 10.1007/s10162-022-00862-2. Epub 2022 Jul 29.
High-intensity sound or blast-induced hearing impairment is a common injury for Service members. Epidemiology studies revealed that the blast-induced hearing loss is associated with the traumatic brain injury (TBI), but the mechanisms of the formation and prevention of auditory injuries require further investigation. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported as a potential treatment strategy for TBI-caused memory deficits; however, there is no study on therapeutics of GLP-1R for blast-induced hearing damage. This paper reports our current study on progressive hearing damage after repeated exposures to low-level blasts in the animal model of chinchilla and the mitigation of hearing damage using liraglutide. Chinchillas were divided into three groups (N = 7 each): blast control, pre-blast treatment, and post-blast treatment. All animals were exposed to six consecutive blasts at the level of 3-5 psi (21-35 kPa) on Day 1. The auditory brainstem response (ABR) was measured on Day 1 (pre- and post-blast) and Days 4, 7, and 14 after blast exposure. Upon the completion of the experiment on Day 14, the brain tissues of animals were harvested for immunofluorescence studies. Significant damage was revealed in blast-exposed chinchillas by increased ABR thresholds, decreased ABR wave I amplitudes, and cell apoptosis in the inferior colliculus in the blast control chinchillas. Treatment with liraglutide appeared to reduce the severity of blast-induced hearing injuries as observed from the drug-treated chinchillas comparing to the blast controls. This study bridges the gap between TBI and hearing impairment and suggests a possible intervention for blast-induced hearing loss for Service members.
高强度声音或爆炸引起的听力损伤是军人常见的损伤。流行病学研究表明,爆炸引起的听力损失与创伤性脑损伤(TBI)有关,但听觉损伤的形成和预防机制仍需进一步研究。利拉鲁肽是一种胰高血糖素样肽-1 受体(GLP-1R)激动剂,已被报道为治疗 TBI 引起的记忆缺陷的潜在治疗策略;然而,尚无关于 GLP-1R 治疗爆炸引起的听力损伤的研究。本文报道了我们在动物模型中研究反复暴露于低水平爆炸后渐进性听力损伤以及利拉鲁肽减轻听力损伤的最新进展。将南美栗鼠分为三组(每组 7 只):爆炸对照组、爆炸前治疗组和爆炸后治疗组。所有动物在第 1 天接受 6 次连续 3-5 磅/平方英寸(21-35 kPa)的爆炸。在第 1 天(爆炸前和爆炸后)和暴露于爆炸后的第 4、7 和 14 天测量听觉脑干反应(ABR)。在第 14 天的实验完成后,采集动物的脑组织进行免疫荧光研究。在爆炸对照组的南美栗鼠中,ABR 阈值升高、ABR 波 I 幅度降低以及下丘脑细胞凋亡表明暴露于爆炸中的南美栗鼠出现明显损伤。与爆炸对照组相比,利拉鲁肽治疗似乎减轻了爆炸引起的听力损伤的严重程度。这项研究填补了 TBI 和听力损伤之间的空白,并为军人的爆炸引起的听力损失提供了一种可能的干预措施。