Fig. 7: Blockade of NLRP3 signaling ameliorates EH and audiovestibular symptoms in sgk1^−/− mice.

a–i The sgk1^+/+ and sgk1^−/− mice were treated with saline or MCC950, and followed by LPS stimulation. a Representative images of EH severity in mid-modiolar cochlear sections, scale bar = 200 μm. b Measurements of IR-L in cochlear half-turns I–IV (n = 5 mice per group). c Representative serial ABR wave recordings and thresholds in response to click sounds (n = 5 mice per group). d ABR thresholds in response to pure tone burst across all frequencies tested (4, 8, 12, 16, 24, and 32 kHz) (n = 5 mice per group). *P indicates p-values for sgk1^−/−+LPS + MCC950 versus sgk1^−/−+LPS; ^#P indicates p-values for sgk1^+/++LPS versus sgk1^−/−+LPS; ^†P indicates p-values for sgk1^+/+ +LPS versus sgk1^−/−+LPS + MCC950. e Representative click-evoked VEMP waves, P1-N1 peak amplitudes, and the P1 (white triangle) and N1 (black triangle) peak latencies of VEMPs at 100 dB nHL (n = 6 mice per group). f Quantification of rotarod test (n = 6 mice per group). g Concentrations of Casp-1 and IL-1β in plasma of treated mice as measured via ELISA (n = 3 mice per group). h Western blot analysis showing NLRP3, SGK1, pro Casp1, Casp-1 p20, pro IL-1β, and cleaved IL-1β levels in the ears (n = 3 mice per group). i Immunofluorescence staining for TUNEL (green) and Myosin VIIa (red) in the basilar membrane, scale bar = 50 μm. Results are presented as mean ± SD. Statistical analyses were carried out via one-way ANOVA for b, c, e–g, and two-way ANOVA for d. EH endolymphatic hydrops, IR-L Increase ratios (IR) of the length of the Reissner’s membrane, ABR auditory brainstem response, VEMPs vestibular-evoked myogenic potentials, P1 positive peak, N1 negative peak, Casp-1 caspase-1. Source data are provided as a Source Data file.