ABSTRACT
On November 8th, 2019, the Cumming School of Medicine at the University of Calgary hosted the 11th annual Leaders in Medicine (LIM) Research Symposium. Dr. Donald A. Redelmeier, Professor at the University of Toronto and Canada Research Chair in Medical Decision Sciences, served as the keynote speaker with a talk entitled "Pitfalls of Reasoning and Clinical Medicine". In addition, there were five oral and 64 poster presentations. These presentations covered topics ranging from health promotion to neuroimaging. The event celebrated the continuing success and diversity of the LIM program and the training of clinician-scientists at the University of Calgary.
ABSTRACT
Sepsis-associated encephalopathy manifesting as delirium is a common problem in critical care medicine. In this study, patients that had delirium due to sepsis had significant cognitive impairments at 12-18 months after hospital discharge when compared with controls and Cambridge Neuropsychological Automated Test Battery-standardized scores in spatial recognition memory, pattern recognition memory, and delayed-matching-to-sample tests but not other cognitive functions. A mouse model of S. pneumoniae pneumonia-induced sepsis, which modeled numerous aspects of the human sepsis-associated multiorgan dysfunction, including encephalopathy, also revealed similar deficits in spatial memory but not new task learning. Both humans and mice had large increases in chemokines for myeloid cell recruitment. Intravital imaging of the brains of septic mice revealed increased neutrophil and CCR2+ inflammatory monocyte recruitment (the latter being far more robust), accompanied by subtle microglial activation. Prevention of CCR2+ inflammatory monocyte recruitment, but not neutrophil recruitment, reduced microglial activation and other signs of neuroinflammation and prevented all signs of cognitive impairment after infection. Therefore, therapeutically targeting CCR2+ inflammatory monocytes at the time of sepsis may provide a novel neuroprotective clinical intervention to prevent the development of persistent cognitive impairments.
