title: Pathogenesis of septic encephalopathy.
abstract: OBJECTIVE
  Septic encephalopathy is a frequent complication in severe sepsis, the pathogenesis and mechanisms of which are not fully understood. Here, we review recent advances in our understanding of septic encephalopathy, from molecular mechanisms to behavioral alterations, from diagnostic tools to potential therapeutic agents.
  
  
  RESULTS
  Recent insights into septic encephalopathy include: microcirculatory failure precedes changes in evoked potential responses; blood-brain barrier alteration is prevented by reducing intercellular adhesion molecule expression and pericyte detachment; reducing infiltration of CD68 macrophages and inhibiting complement activation alleviates neuroinflammation in septic encephalopathy; and reducing mitochondrial dysfunction and inducible nitric oxide synthase expression can restore altered brain function. In addition, other factors such as the circulating levels of growth hormone are independent predictors for mortality and correlate with the severity of sepsis. Similar to humans, septic rats present recognition memory impairment and depressive-like symptoms but not anxiety-like behavior and will serve as efficient models to study the underlying mechanisms of septic encephalopathy.
  
  
  CONCLUSIONS
  Septic encephalopathy is a dynamic disease caused by a complex network of systems and pathways going awry. More insights into the pathogenesis of septic encephalopathy are expected to lead to new cellular and molecular targets, which in turn will permit design of specific septic encephalopathy-alleviating drugs and prevent its negative influence on survival.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pytel
authors.forename: Jessy J
authors.initials: JJ
authors.lastname: Alexander
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology; D020806:Central Nervous System Bacterial Infections / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology*; D003167:Complement Activation; D004195:Disease Models, Animal; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology; D008833:Microcirculation; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*
chemical_list: D015415:Biomarkers