Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

鼓室内脂多糖可提高耳蜗系统对荧光庆大霉素的吸收

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作者:Yongchuan Chai, Weiwei He, Weiqiang Yang, Alisa P Hetrick, Jessica G Gonzalez, Liana Sargsyan, Hao Wu, Timothy T K Jung, Hongzhe Li

Conclusion

In summary, this study suggests that the pathological cochlea is more susceptible to ototoxic drugs, including aminoglycosides, and justified the clinical concern of aminoglycoside ototoxicity in the AOM treatment. Laryngoscope, 131:E2573-E2582, 2021.

Methods

Fluorescently tagged gentamicin (GTTR) was systemically administered to mice with AOM. Iba1-positive macrophage morphology and inner ear cytokine profile were evaluated by immunofluorescence technique and a mouse cytokine array kit, respectively.

Results

We observed characteristic symptoms of AOM in the LPS-treated ears with elevated hearing thresholds indicating a conductive hearing loss. More importantly, the LPS-induced AOM activated cochlear inflammatory responses, manifested by macrophage infiltration, particularly in the organ of Corti and the spiral ligament, in addition to the up-regulation of proinflammatory cytokines. Meanwhile, GTTR uptake in the stria vascularis and sensory hair cells from all the LPS-treated ears was significantly enhanced at 24, 48, and 72-hour post-treatment, as the most prominent enhancement was observed in the 48-hour group.

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