Anton Forsberg1, Simon Cervenka1, Malin Jonsson Fagerlund2,3, Lars S Rasmussen4, Henrik Zetterberg5,6,7, Helena Erlandsson Harris8,9, Pernilla Stridh10, Eva Christensson2,3, Anna Granström2,3, Anna Schening2,3, Karin Dymmel2,3, Nina Knave1, Niccolò Terrando11, Mervyn Maze12, Jacqueline Borg1, Andrea Varrone1, Christer Halldin1, Kaj Blennow5,6, Lars Farde1,13, Lars I Eriksson2,3. 1. Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden. 2. Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden. 3. Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Anesthesia, Center of Head and Orthopedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 5. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. 6. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital of Gothenburg, Mölndal, Sweden. 7. Department of Molecular Neuroscience, University College London Institute of Neurology, London, United Kingdom. 8. Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 9. Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden. 10. Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 11. Department of Anesthesiology, Basic Science Division, Duke University Medical Center, Durham, NC. 12. Department of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, San Francisco, CA. 13. Personalized Healthcare and Biomarkers, AstraZeneca, PET Science Center, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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 [11 C]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 [11 C]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 [11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11 C]PBR28 binding (p = 0.027). INTERPRETATION: 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.
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 [11 C]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 [11 C]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 [11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11 C]PBR28 binding (p = 0.027). INTERPRETATION: 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: Elizabeth Mahanna-Gabrielli; Katie J Schenning; Lars I Eriksson; Jeffrey N Browndyke; Clinton B Wright; Deborah J Culley; Lis Evered; David A Scott; Nae Yah Wang; Charles H Brown; Esther Oh; Patrick Purdon; Sharon Inouye; Miles Berger; Robert A Whittington; Catherine C Price; Stacie Deiner Journal: Br J Anaesth Date: 2019-08-19 Impact factor: 9.166
Authors: Daniel S Albrecht; Anton Forsberg; Angelica Sandström; Courtney Bergan; Diana Kadetoff; Ekaterina Protsenko; Jon Lampa; Yvonne C Lee; Caroline Olgart Höglund; Ciprian Catana; Simon Cervenka; Oluwaseun Akeju; Mats Lekander; George Cohen; Christer Halldin; Norman Taylor; Minhae Kim; Jacob M Hooker; Robert R Edwards; Vitaly Napadow; Eva Kosek; Marco L Loggia Journal: Brain Behav Immun Date: 2018-09-14 Impact factor: 7.217