title: Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning.
abstract: Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway. To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation, BDNF and neurogenesis were assessed at 1, 2 and 3weeks following surgery. Rats displayed changes in exploratory activity shortly after surgery, associated with postoperatively elevated IL-6 plasma levels. Spatial learning and memory were temporarily impaired in the first 2weeks following surgery, whereas non-spatial cognitive functions seemed unaffected. Analysis of brain tissue revealed increased neuroinflammation (IL-1B and microgliosis) 7days following surgery, decreased BDNF levels on postoperative day 14 and 21, and decreased neurogenesis until at least 21days following surgery. These findings indicate that in young adult rats only spatial learning and memory is affected by surgery, suggesting hippocampal dependent cognition is especially vulnerable to surgery-induced impairment. The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact.
authors: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. Electronic address: I.B.Hovens@rug.nl.
authors: Iris B
authors: IB
authors: Hovens
authors: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors: Regien G
authors: RG
authors: Schoemaker
authors: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors: Eddy A
authors: EA
authors: van der Zee
authors: Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Anthony R
authors: AR
authors: Absalom
authors: Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Erik
authors: E
authors: Heineman
authors: Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Barbara L
authors: BL
authors: van Leeuwen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology*; D004660:Encephalitis / Q000150:complications*; D005106:Exploratory Behavior; D007378:Interleukins / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D017628:Microglia / Q000378:metabolism; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007378:Interleukins
keywords: Brain-derived neurotrophic factor; Exploratory behavior; Learning and memory; Neurogenesis; Neuroinflammation; Postoperative cognitive dysfunction; Surgery