Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (10): 3025-3039.doi: 10.4103/NRR.NRR-D-23-01879

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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

Jia Fang1, 2, #, Zhuangzhuang Li1, #, Pengjun Wang1, #, Xiaoxu Zhang1 , Song Mao1 , Yini Li1 , Dongzhen Yu1 , Xiaoyan Li2 , Yazhi Xing1, *, Haibo Shi1 , Shankai Yin1   

  1. 1 Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Otolaryngology Institute of Shanghai Jiao Tong University; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, China;  2 Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Online:2025-10-15 Published:2025-02-09
  • Contact: Yazhi Xing, MD, PhD, yazhi_0807@hotmail.com or dorothy1801@sjtu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81800919 (to YX), 82171140 (to PW) and the International Cooperation and Exchange of the National Natural Science Foundation of China, Nos. 82020108008 (to HS), 81720108010 (to SY).

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Abstract: Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum. However, their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target. In addition, the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure. To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides, we used a C57BL/6J mouse model treated with kanamycin. We found that the mice exhibited auditory deficits following the acute loss of outer hair cells. Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time. Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response, particularly those related to the NLRP3 inflammasome. Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed, accompanied by infiltration of macrophages and the release of proinflammatory cytokines. Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model. These findings suggest that NLRP3 inflammasome–mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration. Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

Key words: degeneration,  hearing loss,  macrophages,  Mcc950,  neuroinflammation,  NLRP3 inflammasome,  ototoxicity,  pyroptosis,  sensorineural hearing loss,  spiral ganglion neuron