Mechanisms of auditory cortex injury and the protective effects of reoxygenation in a rat model of intermittent hypoxia

Intermittent hypoxia associated with obstructive sleep apnea can impair auditory function, but the early mechanisms underlying auditory cortical injury and the extent to which these changes recover after the restoration of normoxia remain unclear. This study investigated the mechanisms underlying auditory cortical injury in a rat model of intermittent hypoxia and evaluated the protective effects of reoxygenation. Adult male Sprague-Dawley rats were assigned to control, intermittent hypoxia, intermittent hypoxia followed by 1 week of normoxic recovery, or control followed by normoxic recovery groups. Short-term intermittent hypoxia caused high-frequency hearing loss and increased spontaneous firing in the primary auditory cortex. After 1 week of normoxic recovery, auditory thresholds and cortical firing rates returned to levels comparable to those in the control group. Glutamate levels did not differ significantly among the groups, whereas γ-aminobutyric acid and 5-hydroxytryptamine levels were elevated in the intermittent hypoxia followed by normoxic recovery group. Intermittent hypoxia increased superoxide dismutase activity, reduced catalase activity, and elevated the levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Normoxic recovery normalized catalase activity and reduced tumor necrosis factor-α and interleukin-6 levels, whereas superoxide dismutase activity and interleukin- 1β levels remained elevated. Metabolomic analysis identified alterations in unsaturated fatty acid biosynthesis, branched-chain amino acid metabolism, ferroptosis-related pathways, redox-related metabolism, and amino acid and protein turnover, several of which persisted after recovery. These findings indicate that acute intermittent hypoxia-induced auditory dysfunction and cortical hyperexcitability are reversible, whereas redox, inflammatory, and metabolic abnormalities recover asynchronously. Persistent molecular disturbances after functional recovery may provide potential targets for further investigation of obstructive sleep apnea-associated central auditory injury.