title: Postoperative cognitive dysfunction and neuroinflammation; Cardiac surgery and abdominal surgery are not the same.
abstract: Postoperative cognitive dysfunction (POCD) is a debilitating surgical complication, with cardiac surgery patients at particular risk. To gain insight in the mechanisms underlying the higher incidence of POCD after cardiac versus non-cardiac surgery, systemic and central inflammatory changes, alterations in intraneuronal pathways, and cognitive performance were studied after cardiac and abdominal surgery in rats. Male Wistar rats were subjected to ischemia reperfusion of the upper mesenteric artery (abdominal surgery) or the left coronary artery (cardiac surgery). Control rats remained naïve, received anesthesia only, or received thoracic sham surgery. Rats were subjected to affective and cognitive behavioral tests in postoperative week 2. Plasma concentrations of inflammatory factors, and markers for neuroinflammation (NGAL and microglial activity) and the BDNF pathway (BDNF, p38MAPK and DCX) were determined. Spatial memory was impaired after both abdominal and cardiac surgery, but only cardiac surgery impaired spatial learning and object recognition. While all surgical procedures elicited a pronounced acute systemic inflammatory response, NGAL and TNFα levels were particularly increased after abdominal surgery. Conversely, NGAL in plasma and the paraventricular nucleus of the hypothalamus and microglial activity in hippocampus and prefrontal cortex on postoperative day 14 were increased after cardiac, but not abdominal surgery. Both surgery types induced hippocampal alterations in BDNF signaling. These results suggest that POCD after cardiac surgery, compared to non-cardiac surgery, affects different cognitive domains and hence may be more extended rather than more severe. Moreover, while abdominal surgery effects seem limited to hippocampal brain regions, cardiac surgery seems associated with more wide spread alterations in the brain.
authors: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: I.B.Hovens@rug.nl.
authors: Iris B
authors: IB
authors: Hovens
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
authors: Department of Cardio-Thoracic Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Massimo A
authors: MA
authors: Mariani
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Aletta D
authors: AD
authors: Kraneveld
authors: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Regien G
authors: RG
authors: Schoemaker
mesh_terms: D000005:Abdomen / Q000601:surgery; D000818:Animals; D001921:Brain / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000523:psychology; D003072:Cognition Disorders / Q000523:psychology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003693:Delirium / Q000209:etiology; D013505:Digestive System Surgical Procedures / Q000009:adverse effects* / Q000523:psychology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D008297:Male; D017628:Microglia / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology; D011183:Postoperative Complications / Q000209:etiology* / Q000473:pathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D065853:Spatial Learning
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein
keywords: Abdominal; Behavior; Brain-derived neurotrophic factor; Cardiac; Cognition; Neurogenesis; Neuroinflammation; Neutrophil gelatinase-associated lipocalin; Postoperative cognitive dysfunction; Surgery