0169 Disruption of Sleep Architecture and Circadian Rhythms Following High Frequency Head Impacts

Abstract

Nearly 25% of mild traumatic brain injury (mTBI) patients report sleep disturbances in the 5 years after injury. Independently of TBI, sleep-wake disturbances are implicated in mood disorders, affect hippocampal signaling pathways, and impair memory consolidation. In this study we determined the affect of multiple mTBI on sleep patterns, brain waves, and circadian rhythms after head impact. To study the effects of multiple TBIs on sleep and circadian rhythms, we use a closed-head mouse model of High Frequency Head Impacts (HFHI): 5 head impacts per day for 6 days. This model uniquely models sub-concussive impacts reported in humans. We see no evidence of cell death, axonal injury, inflammation, or amyloid/tau accumulation, while injured mice display learning and memory deficits and an increase in risk-taking behavior. We found disruptions in circadian mRNA expression at multiple time points post HFHI. Whole brain region RNA analysis of mouse cortex, hippocampus, and hypothalamus for core circadian rhythm genes were conducted at 24 hours and 1-month post HFHI. We found dysregulated expression of core clock genes in these regions both acutely and chronically. We also assessed circadian behavior after injury via wheel running activity, and found changes in activity patterns post injury. To further investigate sleep architecture after HF-HI, animals were implanted with EEG and EMG and monitored at 6-8 weeks post injury. EEG and EMG signals were coded for wake, NREM, and REM. Onemonth post injury, HFHI injured mice showed dysregulated sleep architecture. We also found HFHI altered EEG activity in awake animals. Overall, our data shows a disruption in sleep architecture and in the expression of circadian rhythm genes following HFHI. Given the association of sleep with cognitive and emotional impairments, this study opens up an important avenue of potential therapeutic intervention after injury.