The Effect of Traumatic Brain Injury on Sleep Architecture and Circadian Rhythms in Mice-A Comparison of High-Frequency Head Impact and Controlled Cortical Injury.

Abstract

Simple SummaryTraumatic brain injury (TBI) is a significant risk factor for the development of sleep and circadian rhythm impairments. In order to understand if TBI models with different injury mechanism, severity and pathology have different sleep and circadian rhythm disruptions, we performed a detailed sleep and circadian analysis of the high-frequency head impact TBI model (a mouse model that mimics sports-related head impacts) and the controlled cortical impact TBI model (a mouse model that mimics severe brain trauma). We found that both TBI models disrupt the ability of brain cells to maintain circadian rhythms; however, both injury groups could still maintain circadian behavior patterns. Both the mild head impact model and the severe brain injury model had normal amount of sleep at 7 d after injury; however, the severe brain injury mice had disrupted brain wave patterns during sleep. We conclude that different types of TBI have different patterns of sleep disruptions.Traumatic brain injury (TBI) is a significant risk factor for the development of sleep and circadian rhythm impairments. In this study we compare the circadian rhythms and sleep patterns in the high-frequency head impact (HFHI) and controlled cortical impact (CCI) mouse models of TBI. These mouse models have different injury mechanisms key differences of pathology in brain regions controlling circadian rhythms and EEG wave generation. We found that both HFHI and CCI caused dysregulation in the diurnal expression of core circadian genes (Bmal1, Clock, Per1,2, Cry1,2) at 24 h post-TBI. CCI mice had reduced locomotor activity on running wheels in the first 7 d post-TBI; however, both CCI and HFHI mice were able to maintain circadian behavior cycles even in the absence of light cues. We used implantable EEG to measure sleep cycles and brain activity and found that there were no differences in the time spent awake, in NREM or REM sleep in either TBI model. However, in the sleep states, CCI mice have reduced delta power in NREM sleep and reduced theta power in REM sleep at 7 d post-TBI. Our data reveal that different types of brain trauma can result in distinct patterns of circadian and sleep disruptions and can be used to better understand the etiology of sleep disorders after TBI.