Protective Effects of Molecular Hydrogen on Noise-Induced Auditory and Cognitive Dysfunction

This study aimed to evaluate the protective efficacy and molecular mechanisms of hydrogen (H 2 ) against noise-induced damage across the peripheral and central auditory systems.

Mice were exposed to noise with or without H 2 treatment. Auditory function was assessed using the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Cochlear morphological changes were examined using a scanning electron microscope. Central effects in the inferior colliculus (IC) were evaluated using hematoxylin and eosin staining, transmission electron microscopy, and proteomic analysis. Behavioral changes were measured by using prepulse inhibition (PPI) and shuttle-box tasks.

H 2 significantly attenuated noise-induced ABR threshold shifts ( P < 0.05) and preserved wave I amplitudes at 80 dB (2.69 ± 0.40 vs. 3.57 ± 0.15 μV, P < 0.05). H 2 attenuated noise-induced reduction of DPOAE (16 kHz: 34.40 ± 2.70 vs. 24.67 ± 4.35, P < 0.05) and mitigated outer hair cell (OHC) loss (survival: 89.92% ± 1.23% vs. 82.10% ± 1.6%, all P < 0.05). In the IC, H 2 reduced neuronal pyknosis by 12.6% ( P < 0.05) and preserved the synaptic ultrastructure. Behaviorally, H 2 suppressed the noise-induced elevation of PPI at 75 and 80 dB (75 dB: 40.87% ± 6.32% vs. 58.04% ± 2.47%; 80 dB: 50.01% ± 3.14% vs. 58.04% ± 2.47%, all P < 0.05) and improved performance on the shuttle-box test. Proteomic analysis revealed that H 2 upregulated nicotinamide adenine dinucleotide phosphate hydrogen regeneration-related proteins (e.g., Tigar) and GABAergic synaptic proteins (e.g., Gad1) in the IC.

H 2 exerts a comprehensive neuroprotective effect against noise-induced damage, spanning from OHCs to central synaptic remodeling. This cognitive protection may be mediated by enhancing the antioxidant capacity and restoring the excitation - inhibition balance in the IC.