Environmental Circadian Disruption Increases Stroke Severity and Dysregulates Immune Response

Area of Science:

• Neuroscience
• Chronobiology
• Immunology

Background:

• Chronic circadian rhythm disruption, common in shift work, is linked to increased stroke risk.
• Shift work may exacerbate stroke outcomes through dysregulated immune responses.
• Understanding these links is crucial for developing prevention strategies for shift workers.

Purpose of the Study:

• To investigate how specific schedules of circadian disruption affect inflammatory responses in the brain.
• To determine if circadian disruption increases infarct size after experimentally induced ischemic stroke.
• To explore the role of immune dysregulation in shift work-related stroke outcomes.

Main Methods:

• Mice were subjected to five different lighting schedules, followed by middle cerebral artery occlusion (MCAO) to induce ischemic stroke.
• Infarct volume was measured after a 3-day recovery period.
• Inflammatory responses were assessed by measuring pro- to anti-inflammatory cytokine expression ratios after lipopolysaccharide (LPS) administration.

Main Results:

• Weekly phase advances in lighting schedules significantly increased infarct volume compared to control conditions.
• The observed effects were specific to the direction and schedule of shifts and required multiple shifts.
• Circadian disruption led to dysregulated pro- and anti-inflammatory cytokine expression, indicating a primed inflammatory state.

Conclusions:

• Chronic circadian disruption worsens stroke outcomes in a direction- and schedule-specific manner.
• This worsening is likely due to the priming of inflammatory responses within the brain.
• Interventions targeting shift work scheduling or inflammatory mediators may improve health outcomes for shift workers.