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Mitigation of Hearing Damage After Repeated Blast Exposures in Animal Model of Chinchilla

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Abstract

High-intensity sound or blast-induced hearing impairment is a common injury for Service members. Epidemiology studies revealed that the blast-induced hearing loss is associated with the traumatic brain injury (TBI), but the mechanisms of the formation and prevention of auditory injuries require further investigation. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported as a potential treatment strategy for TBI-caused memory deficits; however, there is no study on therapeutics of GLP-1R for blast-induced hearing damage. This paper reports our current study on progressive hearing damage after repeated exposures to low-level blasts in the animal model of chinchilla and the mitigation of hearing damage using liraglutide. Chinchillas were divided into three groups (N = 7 each): blast control, pre-blast treatment, and post-blast treatment. All animals were exposed to six consecutive blasts at the level of 3–5 psi (21–35 kPa) on Day 1. The auditory brainstem response (ABR) was measured on Day 1 (pre- and post-blast) and Days 4, 7, and 14 after blast exposure. Upon the completion of the experiment on Day 14, the brain tissues of animals were harvested for immunofluorescence studies. Significant damage was revealed in blast-exposed chinchillas by increased ABR thresholds, decreased ABR wave I amplitudes, and cell apoptosis in the inferior colliculus in the blast control chinchillas. Treatment with liraglutide appeared to reduce the severity of blast-induced hearing injuries as observed from the drug-treated chinchillas comparing to the blast controls. This study bridges the gap between TBI and hearing impairment and suggests a possible intervention for blast-induced hearing loss for Service members.

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Acknowledgements

We gratefully acknowledge Dr. Emi Kiyotake, Dr. John Clegg, and Dr. Michael Detamore from Stephenson School of Biomedical Engineering at the University of Oklahoma for sharing their equipment, environment, and technology for the IF study presented in this paper.

Funding

This study was supported by the Department of Defense (DOD) grant W81XWH-19–1-0469.

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Correspondence to Rong Z. Gan.

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The authors declare no competing interests.

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Appendix

Appendix

Figure 10 presents the screenshots of the ABR waveforms measured at different epoch numbers ranging from 16 to 908. The waveforms were recorded at 8 kHz, 95 dB. As can be seen from the figure, some random fluctuations were observed at 16, but it was hard to observe changes with the epoch number changing from 142 to 908. Therefore, 150 was an adequate number of sweeps to produce replicable ABR waveforms and allowed for threshold and peak picking analysis in our experimental paradigm.

Fig. 10
figure 10

Screenshots of ABR waveforms measured with different numbers of epochs. The ABR was measured at 8 kHz, 95 dB

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Jiang, S., Welch, P., Sanders, S. et al. Mitigation of Hearing Damage After Repeated Blast Exposures in Animal Model of Chinchilla. JARO 23, 603–616 (2022). https://doi.org/10.1007/s10162-022-00862-2

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  • DOI: https://doi.org/10.1007/s10162-022-00862-2

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