Mild traumatic brain injury produces persistent wake-state instability and EEG slowing despite carbon monoxide neuroprotection.

Individuals who experience mild traumatic brain injury (mTBI) frequently report persistent sleep-wake disturbances that impair daytime function and recovery. However, the physiological nature of these disturbances remains incompletely understood. Using a closed-head lateral-impact model of single and repeated mTBI in mice, we examined the acute and chronic effects of injury on EEG activity and behavioral state organization. Although mTBI did not alter the total amount of time spent awake or asleep, both single and repeated injuries produced a marked and persistent fragmentation of wakefulness that remained evident for up to 12 weeks after injury. Spectral analysis further revealed increased low-theta (4-8 Hz) activity during wakefulness, consistent with reduced cortical activation and impaired arousal stability. Because low concentrations of carbon monoxide (CO) have been reported to exert neuroprotective effects in models of brain injury, we also examined whether inhaled CO could mitigate these abnormalities. While CO reduced acute injury-associated measures and glial stress marker expression, it did not rescue wake fragmentation or EEG spectral changes at the time points tested. Together, these findings identify persistent wake-state instability as a key consequence of mTBI and suggest that mechanisms governing the maintenance of consolidated wakefulness remain disrupted despite attenuation of acute injury-related pathology.