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Background Sepsis-associated brain dysfunction (SABD) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome. It is associated with high mortality and a majority of survivors suffer long-term neurological consequences. Sleep is commonly affected in sepsis and there is a strong correlation between its impairment and development of other complications or increased mortality in sepsis patients. Here, we investigate the effects of sepsis on brain activity patterns in order to better understand possible sources of sleep-wake disturbances associated with severe systemic inflammation. Methods We studied the effects of high LPS doses (10mg/kg) on oscillatory brain states in an acute rat model of sepsis under urethane anaesthesia, which maintains REM- and NREM sleep-like states. Twelve Long-Evans rats (6 LPS, 6 controls) were implanted with eight independently movable tetrodes in the dorsal hippocampus. Baseline LFP activity was recorded for 3 hours after saline injection, followed by another 3 hours after LPS or saline injection. REM and NREM were automatically classified based on LFP activity and quantified. Within- and between-state dynamics were analysed using a 2-D state space approach based on spectral power ratios. Aperiodic and periodic components of the power spectrum were quantified for each state. Blood serum samples and brains were collected for IL-1β quantification and histological verification of electrode placement. Results Soon after LPS injection we observed a robust fragmentation of both oscillatory states resulting in a three-fold increase in the number of state transitions that lasted for several hours, although the overall time spent in either state did not change. Analysis of power spectra showed opposing shifts in low frequency oscillations (1–9 Hz) in REM and NREM that resulted in increased similarity between both states in 2-D state space. Conclusions The observed increased spectral similarity between REM and NREM and increased instability within the states may point to a mechanism underlying the severe sleep fragmentation described both in sepsis patients and in SABD animal models. |
