Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice

Yufeng Li; Huiqian Yu; Xuehua Zhou; Lin Jin; Wen Li; Geng-Lin Li; Xia Shen

doi:10.3389/fnins.2022.945277

Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice

Front Neurosci. 2022 Jul 14:16:945277. doi: 10.3389/fnins.2022.945277. eCollection 2022.

Authors

Yufeng Li¹, Huiqian Yu², Xuehua Zhou¹, Lin Jin¹, Wen Li², Geng-Lin Li^{2

3}, Xia Shen¹

Affiliations

¹ Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China.
² ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
³ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.

Abstract

Objectives: 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.

Materials and methods: 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.

Results: 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, 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), and 32 kHz (41.25 ± 2.31 vs. 54.41 ± 2.94 dB, P = 0.0028) on P30, caused ribbon synapse loss on P15 (13.10 ± 0.43 vs. 10.78 ± 0.52, P = 0.0039) and P30 (11.24 ± 0.56 vs. 8.50 ± 0.84, P = 0.0141), and degenerated spiral ganglion neuron (SGN) nerve fibers on P30 (110.40 ± 16.23 vs. 55.04 ± 8.13, P = 0.0073). In addition, the V _half of calcium current become more negative (-21.99 ± 0.70 vs. -27.17 ± 0.60 mV, P < 0.0001), exocytosis was reduced (105.40 ± 19.97 vs. 59.79 ± 10.60 fF, P < 0.0001), and Lpo was upregulated (P = 0.0219) in sevoflurane group than those in control group. N-acetylcysteine (NAC) reversed hearing impairment induced by sevoflurane.

Conclusion: 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.

Keywords: hair cells; hearing impairment; oxidative stress; ribbon synapse; sevoflurane; spiral ganglion neuron nerve fiber.