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

Abstract

Abstract Introduction Mild Traumatic Brain Injury (mTBI) can cause a broad array of behavioral problems including cognitive and emotional deficits. Sleep disturbances including disrupted sleep latency and efficiency are common amongst human mTBI patients. Crucially, sleep plays a key role in hippocampal learning and memory consolidation, yet the contribution of single and repetitive mTBIs influencing sleep related cognitive outcomes remains unclear. Methods To study the effect of repetitive mTBI on sleep and circadian rhythms, C57Bl/6 mice underwent sham or High Frequency-Head Impact (HF-HI, 30 closed head impacts, 5/per day for 6-days) procedures before brains were assessed at 1d, 1m and 2m using a combination of molecular neurobiology (RNA/protein), EEG/ EMG recordings and behavioral analysis. Results HF-HI induces learning and memory deficits in the Barnes and T-Maze at both 1d and 1m post injury, in the absence of axonal injury, inflammation, or protein deposition. Disruptions in circadian mRNA expression was identified at multiple time points post HF-HI. RNA analysis of mouse cortex, hippocampus, and hypothalamus for core circadian rhythm genes (Bmal1, Clock, Cryptochrome 2, Period1 and Period 2) was conducted at 1d and 1m post HF-HI. We found dysregulated expression of these core biological clock genes in these regions at both time points. Furthermore, we find distinct changes to sleep architecture chronically post injury. Animals were implanted with EEG and EMG for monitoring at 2m post injury. EEG and EMG signals were coded for wake, NREM, and REM. One-month post injury, HFHI injured mice showed dysregulated sleep architecture compared to sham mice, while both groups had the same total sleep time. We also demonstrate that HF-HI alters EEG activity in awake animals. Conclusion Overall, our data shows disruptions in both sleep architecture and expression of circadian rhythm genes following HF-HI. This opens up an important avenue of potential therapeutic intervention following injury. Support If deficits in sleep and circadian rhythms can be rescued after mTBI, it may assist in improving symptoms and chronic outcomes after injury.