Li Yufeng, Yu Huiqian, Zhou Xuehua, Jin Lin, Li Wen, Li Geng-Lin, Shen Xia
Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China.
ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Front Neurosci. 2022 Jul 14;16:945277. doi: 10.3389/fnins.2022.945277. eCollection 2022.
This study aims to investigate the effects of multiple sevoflurane exposures in neonatal mice on hearing function in the later life and explores the underlying mechanisms and protective strategies.
Neonatal Kunming mice were exposed to sevoflurane for 3 days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests, immunofluorescence, patch-clamp recording, and quantitative real-time PCR were performed to observe hearing function, hair cells, ribbon synapses, nerve fibers, spiral ganglion neurons, and oxidative stress.
Compared to control group, multiple sevoflurane exposures during the neonatal time significantly elevated ABR thresholds at 8 kHz (35.42 ± 1.57 vs. 41.76 ± 1.97 dB, = 0.0256), 16 kHz (23.33 ± 1.28 vs. 33.53 ± 2.523 dB, = 0.0012), 24 kHz (30.00 ± 2.04 vs. 46.76 ± 3.93 dB, = 0.0024), and 32 kHz (41.25 ± 2.31 vs. 54.41 ± 2.94 dB, = 0.0028) on P30, caused ribbon synapse loss on P15 (13.10 ± 0.43 vs. 10.78 ± 0.52, = 0.0039) and P30 (11.24 ± 0.56 vs. 8.50 ± 0.84, = 0.0141), and degenerated spiral ganglion neuron (SGN) nerve fibers on P30 (110.40 ± 16.23 vs. 55.04 ± 8.13, = 0.0073). In addition, the V of calcium current become more negative (-21.99 ± 0.70 vs. -27.17 ± 0.60 mV, < 0.0001), exocytosis was reduced (105.40 ± 19.97 vs. 59.79 ± 10.60 fF, < 0.0001), and was upregulated ( = 0.0219) in sevoflurane group than those in control group. -acetylcysteine (NAC) reversed hearing impairment induced by sevoflurane.
The findings suggest that multiple sevoflurane exposures during neonatal time may cause hearing impairment in adult mice. The study also demonstrated that elevated oxidative stress led to ribbon synapses impairment and SGN nerve fibers degeneration, and the interventions of antioxidants alleviated the sevoflurane-induced hearing impairment.
本研究旨在探讨新生小鼠多次暴露于七氟醚对其后期听力功能的影响，并探究其潜在机制及保护策略。
将新生昆明小鼠暴露于七氟醚3天。进行听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）测试、免疫荧光、膜片钳记录及实时定量PCR，以观察听力功能、毛细胞、带状突触、神经纤维、螺旋神经节神经元及氧化应激情况。
与对照组相比，新生期多次暴露于七氟醚显著提高了P30时8 kHz（35.42±1.57 vs. 41.76±1.97 dB，P = 0.0256）、16 kHz（23.33±1.28 vs. 33.53±2.523 dB，P = 0.0012）、24 kHz（30.00±2.04 vs. 46.76±3.93 dB，P = 0.0024）和32 kHz（41.25±2.31 vs. 54.41±2.94 dB，P = 0.0028）的ABR阈值，导致P15（13.10±0.43 vs. 10.78±0.52，P = 0.0039）和P30（11.24±0.56 vs. 8.50±0.84，P = 0.0141）时带状突触损失，以及P30时螺旋神经节神经元（SGN）神经纤维退化（110.40±16.23 vs. 55.04±8.13，P = 0.
