Shi Mengwen, Wang Ye, Yang Huiwen, Lai Chengcai, Yu Jintao, Sun Yu
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
Heliyon. 2024 Aug 31;10(18):e37223. doi: 10.1016/j.heliyon.2024.e37223. eCollection 2024 Sep 30.
Radiotherapy is a crucial treatment for head and neck malignancies, but it can sometimes cause sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensory neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of heterozygous 8-week-old Cx3cr1 male mice were irradiated with 30Gy of X-rays and biological samples were collected on days 1, 7, and 10 after irradiation. Auditory brainstem responses were used to assess auditory function in the mice. Changes in basilar membrane hair cells, spiral ganglion neurons (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cochlear tissue. The results showed no significant hair cell loss after a single high dose of radiation. However, the mice developed pantonal hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence showed decreased neurofilament expression. The number of macrophages in the inner ear reduced over time. RT-qPCR showed that cochlear inflammatory factors and chemokines were briefly upregulated on day 1st after irradiation and then decreased over time. In conclusion, high-dose irradiation causes acute SNHL that is not associated with hair cell loss and may be related to SGN changes. Radiation-induced SNHL is associated with a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two remains to be investigated.
放射治疗是头颈部恶性肿瘤的关键治疗方法，但有时会导致感音神经性听力损失（SNHL）。辐射暴露后内耳免疫微环境和感觉神经上皮的变化仍知之甚少。本研究调查了高剂量照射后内耳的耳蜗形态和巨噬细胞。对8周龄杂合Cx3cr1雄性小鼠的头部进行30Gy的X射线照射，并在照射后第1、7和10天收集生物样本。使用听觉脑干反应评估小鼠的听觉功能。采用苏木精-伊红（HE）染色和免疫荧光染色观察基底膜毛细胞、螺旋神经节神经元（SGN）和内耳巨噬细胞的变化。通过耳蜗组织中的定量实时逆转录-聚合酶链反应（RT-qPCR）检测内耳中炎症介质的表达。结果显示，单次高剂量辐射后毛细胞无明显损失。然而，在第10天小鼠出现全频听力损失，此时HE染色显示SGN萎缩，免疫荧光显示神经丝表达降低。内耳巨噬细胞数量随时间减少。RT-qPCR显示，耳蜗炎症因子和趋化因子在照射后第1天短暂上调，然后随时间下降。总之，高剂量照射导致急性SNHL，这与毛细胞损失无关，可能与SGN变化有关。辐射诱导的SNHL与耳蜗巨噬细胞减少和免疫微环境变化有关，但两者之间的关系仍有待研究。
