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A delayed pharmacological treatment strategy attenuates noise-induced tinnitus in rats
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  • Published: 03 March 2026

A delayed pharmacological treatment strategy attenuates noise-induced tinnitus in rats

  • Jianzhong Lu1,
  • Xiaoping Du1,
  • Zachary Yokell1,
  • Qunfeng Cai1,
  • Weihua Cheng1,
  • Don Nakmali1,
  • Wei Li1,
  • Xiangping Huang1,
  • Richard D. Kopke1 &
  • …
  • Matthew B. West1 

Scientific Reports , Article number:  (2026) Cite this article

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Subjects

  • Auditory system
  • Neurophysiology

Abstract

It is widely accepted that tinnitus arises from maladaptive neuroplasticity in the central auditory system, which compensates for reduced peripheral input; notably, the loss of inner hair cell (IHC) synapses is considered a key underlying factor. IHC synapses can immediately and permanently degenerate after noise exposure, independent of hair cell loss, whereas the cell bodies and central projections of cochlear neurons can survive for months to years, providing an extended therapeutic window for improving afferent input through synapse regeneration. Using NHPN-1010 (a combination of 2,4-disulfophenyl-N-tert-butylnitrone and N-acetylcysteine), we propose a delayed treatment strategy (≥ 4 weeks after trauma) for noise-induced tinnitus (NIT) in rats. NHPN-1010 enhanced gap-prepulse inhibition of acoustic startle responses—indicative of diminished tinnitus-like deficits—coupled with a concomitant upregulation of GABAergic inhibition in the dorsal cochlear nucleus, relative to vehicle alone (saline). Furthermore, NHPN-1010, compared to saline, led to increased wave-I amplitudes of auditory brainstem responses, the effect accompanied by a corresponding rise in the number of presynaptic ribbons in IHCs. Our findings suggest that NHPN-1010 plays a therapeutic role in NIT by promoting cochlear synaptogenesis and normalizing central auditory signaling.

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Data availability

All data are available from the corresponding author.

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Acknowledgements

This research was supported by The Oklahoma Center for the Advancement of Science and Technology (OCAST) grant # AR20-014.

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  1. Hough Ear Institute, Oklahoma City, OK, 73112, USA

    Jianzhong Lu, Xiaoping Du, Zachary Yokell, Qunfeng Cai, Weihua Cheng, Don Nakmali, Wei Li, Xiangping Huang, Richard D. Kopke & Matthew B. West

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J.L., X.D., R.D.K. and M.B.W. designed research; J.L., X.D., Z.Y., Q.C., W.C., D.N., W.L. and X.H. performed research; J.L. analyzed data; J.L., X.D. and M.B.W. wrote the paper.

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Correspondence to Matthew B. West.

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Richard D. Kopke has a financial interest in Otologic Pharmaceutics, Inc. All other authors declare no competing interests.

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Lu, J., Du, X., Yokell, Z. et al. A delayed pharmacological treatment strategy attenuates noise-induced tinnitus in rats. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40960-2

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  • Received: 25 June 2025

  • Accepted: 17 February 2026

  • Published: 03 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-40960-2

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Keywords

  • auditory brainstem response
  • acoustic startle response
  • noise-induced tinnitus
  • ribbon synapse
  • GABAAR
  • NHPN-1010
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