Journal
CHEST
Volume 140, Issue 3, Pages 580-585Publisher
ELSEVIER SCIENCE BV
DOI: 10.1378/chest.10-3065
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Funding
- Foundation for Anesthesia Education and Research
- National Institutes of Health [AG034257]
- Northern Ireland Public Health Agency Research and Development Division Translational Research Group for Critical Care
- US Department of Veterans Affairs Clinical Science Research and Development Service [AG027472]
- US Department of Veterans Affairs Tennessee Valley Geriatric Research, Education, and Clinical Center
- AstraZeneca
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Delirium is a frequent form of acute brain dysfunction in patients who are critically ill and is associated with poor clinical outcomes, including a critical illness brain injury that may last for months to years. Despite widespread recognition of significant adverse outcomes, pharmacologic approaches to prevent or treat delirium during critical illness remain unproven. We hypothesize that commonly prescribed statin medications may prevent and treat delirium by targeting molecular pathways of inflammation (peripheral and central) and microglial activation that are central to the pathogenesis of delirium. Systemic inflammation, a principal mechanism of injury, for example, in sepsis, acute respiratory distress syndrome, and other critical illnesses, can cause neuronal apoptosis, blood-brain barrier injury, brain ischemia, and microglial activation. We hypothesize that the known pleiotropic effects of statins, which attenuate such neuroinflammation, may redirect microglial activation and promote an antiinflammatory phenotype, thereby offering the potential to reduce the public health burden of delirium and its associated long-term cognitive injury. CHEST 2011; 140(3):580-585
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