title: The immune response of the human brain to abdominal surgery.
abstract: OBJECTIVE
  Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.
  
  
  METHODS
  Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.
  
  
  RESULTS
  Patients showed a global downregulation of gray matter [11C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [11C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11C]PBR28 binding (p = 0.027).
  
  
  CONCLUSIONS
  This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582.
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Forsberg
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Cervenka
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Jonsson Fagerlund
authors.affiliation: Department of Anesthesia, Center of Head and Orthopedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars S
authors.initials: LS
authors.lastname: Rasmussen
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital of Gothenburg, Mölndal, Sweden.|Department of Molecular Neuroscience, University College London Institute of Neurology, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.|Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Erlandsson Harris
authors.affiliation: Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pernilla
authors.identifier: http://orcid.org/0000-0003-4855-0039
authors.initials: P
authors.lastname: Stridh
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Christensson
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Granström
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Schening
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Dymmel
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Knave
authors.affiliation: Department of Anesthesiology, Basic Science Division, Duke University Medical Center, Durham, NC.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Terrando
authors.affiliation: Department of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, San Francisco, CA.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.|Personalized Healthcare and Biomarkers, AstraZeneca, PET Science Center, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden.|Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Eriksson
mesh_terms: D000005:Abdomen / Q000601:surgery; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000503:physiopathology; D015536:Down-Regulation; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011468:Prostatectomy / Q000009:adverse effects*
chemical_list: D015415:Biomarkers