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Sleep Fragmentation, Electroencephalographic Slowing, and Circadian Disarray in a Mouse Model for Intensive Care Unit

Elzbieta Dulko1, Michal Jedrusiak1, Hari P Osuru1

  • 1From the Departments of Anesthesiology.

Anesthesia and Analgesia
|May 16, 2023
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Summary

Anesthesia, Surgery, and simulated ICU conditions (ASI) in aged mice induced sleep fragmentation, EEG slowing, and circadian disruption, validating a new animal model for delirium. This model mimics changes seen in intensive care unit (ICU) patients with delirium.

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Area of Science:

  • Neuroscience
  • Sleep Medicine
  • Critical Care Medicine

Background:

  • Delirium is a common complication in intensive care unit (ICU) patients.
  • Existing animal models for delirium have limitations in fully replicating the complex ICU environment.
  • Sleep fragmentation, electroencephalographic (EEG) slowing, and circadian rhythm disruption are hallmarks of delirium in ICU patients.

Purpose of the Study:

  • To validate a previously developed animal model for delirium.
  • To test the hypothesis that Anesthesia, Surgery, and simulated ICU conditions (ASI) induce delirium-like symptoms in aged mice.
  • To assess sleep fragmentation, EEG slowing, and circadian disarray in mice exposed to ASI.

Main Methods:

  • Forty-one aged mice were used, with EEG electrodes implanted.
  • Mice were randomized into ASI (laparotomy, anesthesia, simulated ICU) and control groups.
  • Sleep patterns, EEG dynamics, and hippocampal circadian gene expression were analyzed using t-tests and RM ANOVA.

Main Results:

  • ASI mice exhibited significantly increased arousals and EEG slowing compared to controls.
  • EEG slowing in ASI mice was associated with increased quiet wakefulness.
  • ASI mice showed disrupted circadian rhythms, with altered sleep durations during dark phases and reduced expression of key circadian genes (BMAL1, CLOCK).

Conclusions:

  • The ASI mouse model successfully replicated EEG and circadian changes observed in ICU patients with delirium.
  • This validated animal model provides a valuable tool for further research into the neurobiology of delirium.
  • The findings support the use of this model to characterize delirium mechanisms and test potential interventions.