Fig. 4

SPT-2101 prevents LPS-induced cochlear injury and hearing loss. (A) Experimental design scheme: LPS was injected IP at 5 and 10 mg/kg on two consecutive days. SPT-2101 (SPT) or its vehicle were intratympanically injected 72 h before LPS. Auditory brainstem responses (ABR) were recorded at the before (baseline) and 72 h after the first LPS challenge. At this endpoint, a dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI; 45 cycles, IV injection of contrast agent at cycle 7) was performed to determine BLB permeability. (B) Evolution of signal enhancement (mean ± SE) along the DCE-MRI performed 72 h after LPS, in control (white circles, n = 16), LPS (red circles, n = 16), LPS plus SPT (green triangles, n = 14) and LPS plus vehicle (orange triangles, n = 14) experimental groups. (C) T1-weighted horizontal images acquired at DCE-MRI 30th cycle in representative rats from LPS + vehicle and LPS + SPT groups. A magnification of the cochlea is shown in the white square. (D) Signal enhancement (mean ± SE) obtained in cycle 30th in the aforementioned experimental groups. Rats injected with LPS and treated with systemic dexamethasone for one (light blue, n = 9) or three (dark blue, n = 5) consecutive days after challenge, were also included. Statistically significant differences were calculated using one-way ANOVA (***p < 0.001, compared to controls; #p < 0.05, ###p < 0.001, compared to LPS + vehicle). (E) ABR thresholds (mean ± SE, in dB SPL) before and 72 h after LPS injection in rats treated with intratympanic SPT (green, n = 8) or vehicle (orange, n = 11). Statistically significant differences were calculated using the Mann-Whitney test (*p < 0.05)