Fig. 3 | Nature Communications

Fig. 3

From: Cisplatin is retained in the cochlea indefinitely following chemotherapy

Fig. 3

The cochlear stria vascularis accumulates high levels of cisplatin, resulting in its dysfunction. a A cross-sectional illustration of cochlear architecture. The three regions of the cochlea: stria vascularis, organ of Corti and spiral ganglion, microdissected for ICP-MS analysis are indicated by dashed red lines. Endolymph fills the blue shaded region. IHC inner hair cell, OHC outer hair cell. b Platinum concentrations in microdissected cochlear regions in the first 24 h following a single i.p. injection of cisplatin. Cisplatin readily distributes throughout these cochlear regions within the first hour. Platinum concentrations are normalized to sulfur content, a surrogate for total tissue quantity51. n = 3–4 mice per time point. Statistical significance is displayed for stria vascularis values as compared to the other two cochlear regions. Two-way ANOVA followed by the Holm–Šidák multiple comparisons test was used to determine significance. c Concentrations of platinum in cochlear regions throughout the complete cisplatin regimen. Platinum progressively accumulates in all three regions, but most significantly in stria vascularis. n = 3 mice per time point. Statistical significance is displayed for stria vascularis values as compared to other two regions. Two-way ANOVA followed by the Holm–Šidák multiple comparisons test was used to determine significance. d Concentrations of platinum in cochlear regions at the end of the cisplatin regimen and following a subsequent 60-day recovery. All regions show a decrease in platinum concentrations. n = 4 mice per group. Unpaired two-tailed t-tests were used to determine significance. e Representative low-magnification confocal slices from cochlear cryosections of mice treated with a full regimen of BODIPY FL-cisplatin or the control (no cisplatin) conjugate BODIPY FL-Boc. SG spiral ganglion, OC organ of Corti, SV stria vascularis, IS interscalar septum. Scale bar = 100 µm. f Representative maximum intensity projections of thin confocal stacks of the stria vascularis only. Scale bar = 50 µm. g Representative maximum intensity projections of confocal stacks of organ of Corti whole mounts. Scale bar = 25 µm. h Endocochlear potentials (EPs) measured in the endolymph following cisplatin treatment. EPs decline at 24 h after cisplatin but recover somewhat by the end of the regimen. However, 60 days after cessation of cisplatin administration, EPs are still significantly reduced. n = 3–6 mice per group; data points represent individual mice. Unpaired two-tailed t-tests were used to determine significance. Data are expressed as mean ± s.e.m. ns not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001

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