title: Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats.
abstract: Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We hypothesized that regional differences in postoperative neuroinflammation in the brain may underlie variation in postoperative cognitive impairment. We aimed to investigate this hypothesis in a rat-model for POCD, by analyzing postoperative impairment in behavioral task performance and microglial activation in related brain areas. We subjected 25 months old Wistar rats to surgery and assessed spatial learning and memory, object and location recognition, reversal learning and exploratory behavior in the second postoperative week. The number and morphology of microglia were analyzed in the hippocampus, prefrontal cortex, striatum and amygdala on postoperative day 14. Control groups consisted of 3 and 25 months old rats that did not undergo surgery. We observed age related impairment in learning, memory and behavior, which was aggravated following surgery. Additionally, in old rats surgery was associated with signs of classical microglial activation in brain areas related to the impaired cognitive functions. These outcomes suggest that indeed neuroinflammation may be involved in POCD. Moreover, effects of age and surgery on cognition and microglial morphology seem to be area specific and hence cannot be generalized to the whole brain. This underpins the importance for expanding the research of POCD beyond the hippocampus.
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. Electronic address: I.B.Hovens@rug.nl.
authors.forename: Iris B
authors.initials: IB
authors.lastname: Hovens
authors.affiliation: Brain Physiology Unite, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: van Leeuwen
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Surgery & Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Csaba
authors.initials: C
authors.lastname: Nyakas
authors.affiliation: Brain Physiology Unite, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary.
authors.forename: Erik
authors.initials: E
authors.lastname: Heineman
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology; D017628:Microglia / Q000502:physiology*; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology; D065853:Spatial Learning / Q000502:physiology
keywords: Aging; Behavior; Learning and memory; Microglia; Postoperative cognitive dysfunction