title: Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction.
abstract: OBJECTIVE
  Postoperative cognitive dysfunction (POCD) is a well recognized perioperative syndrome, with approximately 15% of patients over the age of 60 years displaying objectively measured decrease in cognitive function as a consequence of anesthesia and surgery. The exact cause, however, remains unknown. This review aims to update anesthesiologists on the recent advancements in the understanding of the pathophysiology of POCD.
  
  
  RESULTS
  Recent evidence suggests that the observed predilection to POCD is likely mediated by a neuro-inflammatory response - with surgery being a major contributing factor. The blood-brain barrier, a highly specialized endothelial layer, is exquisitely sensitive to an inflammatory insult and implicated in the cause of other neurocognitive syndromes also characterized by neuro-inflammation such as cerebral malaria. Inflammatory changes may disrupt the blood-brain barrier and facilitate migration of macrophages into the brain, damaging synapses and neurones and ultimately lead to POCD. This review explores the important question of causality - the potential relationship between inflammation, endothelial dysfunction, and postoperative cognitive decline.
  
  
  CONCLUSIONS
  Recent research points to a central role of a neuro-inflammatory cascade in POCD, with endothelial dysfunction potentially aggravating the insult. Investigating the genomic and molecular mechanisms that underlie the intervariation in the inflammatory response to surgery, improving the identification of appropriate endothelial and inflammatory biomarkers, and developing endothelial modulatory and anti-inflammatory (prevention and resolution) strategies are key areas of future translational research. This is important as the elderly, who show increased susceptibility to this and other perioperative illness syndromes, represent an ever-increasing proportion of patients presenting for surgery.
authors.affiliation: aDepartment of Anaesthesia and Pain Medicine, Peter MacCallum Cancer Center bDepartment of Anaesthesia, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Riedel
authors.forename: Kimberley
authors.initials: K
authors.lastname: Browne
authors.forename: Brendan
authors.initials: B
authors.lastname: Silbert
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018916:Blood-Aqueous Barrier / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D019990:Perioperative Care; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology*
chemical_list: D000893:Anti-Inflammatory Agents