Figure 4
Effect of ISRIB on ABR threshold and suprathreshold wave-I amplitude in noise-induced cochlear synaptopathy. ABR threshold (A,B), threshold shift (C,D) and suprathreshold Wave-I amplitude (E,F) and shift (G,H) were measured in female (top) and male (bottom) CBA/J mice after a single intraperitoneal dose of ISRIB (red) or vehicle (black) and exposure to 97.8 dB, 8–16 kHz octave-band noise (solid lines), as well in non-noise-exposed control mice (dotted lines). 21 days after noise exposure, there were no significant differences in ABR threshold (A,B) or threshold shift (C,D) between mice pretreated with ISRIB (red) or vehicle (black). ISRIB-treated male mice had statistically significant improvement in wave-I amplitude (F) and noise-induced wave-I shift (H) compared to vehicle-treated male mice. Female mice (E,G) showed no improvement in wave-I amplitude with ISRIB treatment. Data represent means ± s.e. *p < 0.05; **p < 0.01, with exact p values provided as indicated (Student’s t test comparing ISRIB-(red) and vehicle-(black) treated, noise-exposed groups at individual frequencies). (I) Representative ABR traces at baseline (black) and post-noise-exposure (PNE) day 1 (PNE1, red) and PNE21 (blue) are shown, demonstrating reduction of wave-I amplitude (peak-to-trough, indicated for baseline reference traces by grey boxes) at PNE1 in noise-exposed mice (red, middle and right). Partial recovery at PNE21 was seen in vehicle-treated mice (blue, middle). Full recovery was seen in an ISRIB-treated male mouse (blue, bottom right), compared with no recovery in an ISRIB-treated female mouse (blue, top right). Control animals (left) did not undergo noise exposure. Traces were high-pass filtered at 200 Hz to eliminate baseline drift and normalized to baseline wave-I amplitude for each mouse (Scale bar: vertical, normalized wave-I amplitude axis; horizontal, time).
