title: Prior infection exacerbates postoperative cognitive dysfunction in aged rats.
abstract: Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activity, neurogenesis, and concentrations of IL-6, IL-12, IL1B, and brain-derived neurotropic factor on postoperative day 14 were determined. Rats still showed signs of increased neuroinflammatory activity, as well as cognitive and behavioral changes, 3 wk after the symptoms of infection had subsided. Rats that had experienced infection before surgery exhibited a more generalized and exacerbated postoperative cognitive impairment compared with healthy surgery rats, as well as a prolonged increase in systemic cytokine levels and increased microglial activation in the hippocampus and prefrontal cortex. These findings support the hypothesis that an infection before surgery under general anesthesia exacerbates POCD. Future studies are necessary to determine whether the found effects are aging specific and to investigate the magnitude and time course of this effect in a controlled manner.
authors.affiliation: Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands; Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and I.B.Hovens@rug.nl.
authors.forename: Iris B
authors.initials: IB
authors.lastname: Hovens
authors.affiliation: Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: van Leeuwen
authors.affiliation: Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands; Behavioral Physiology Research Unite, Department of Morphology and Physiology, Health Science Faculty, Semmelweis University, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Nyakas
authors.affiliation: Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Erik
authors.initials: E
authors.lastname: Heineman
authors.affiliation: Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands;
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee
authors.affiliation: Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands;
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000367:Age Factors; D000375:Aging; D000768:Anesthesia, General; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D005106:Exploratory Behavior; D006120:Grooming; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008568:Memory; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009175:Mycoplasma Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D045803:Mycoplasma pulmonis / Q000276:immunology / Q000472:pathogenicity*; D009479:Neuropeptides / Q000378:metabolism; D011183:Postoperative Complications / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D017208:Rats, Wistar; D012307:Risk Factors; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000089622:Doublecortin Domain Proteins; D018836:Inflammation Mediators; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: brain-derived neurotropic factor; infection; learning and memory; neuroinflammation; postoperative cognitive dysfunction