Title |
The immune response of the human brain to abdominal surgery
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Published in |
Annals of Neurology, April 2017
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DOI | 10.1002/ana.24909 |
Pubmed ID | |
Authors |
Anton Forsberg, Simon Cervenka, Malin Jonsson Fagerlund, Lars S. Rasmussen, Henrik Zetterberg, Helena Erlandsson Harris, Pernilla Stridh, Eva Christensson, Anna Granström, Anna Schening, Karin Dymmel, Nina Knave, Niccolò Terrando, Mervyn Maze, Jacqueline Borg, Andrea Varrone, Christer Halldin, Kaj Blennow, Lars Farde, Lars I. Eriksson |
Abstract |
Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. While 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. Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative day 3-4 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. Patients showed a global down-regulation of GM [(11) C]PBR28 binding of 26±26% (mean±SD) at 3-4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the pro-inflammatory marker TNF-α in blood displayed a reduction (41±39%) on the 3-4(th) postoperative day, corresponding to changes in [(11) C]PBR28 VT . Change in Stroop color word cognitive test performance between postoperative day 3-4 and 3 months correlated to change in [(11) C]PBR28 binding (p=0.027). 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 post-surgical impairments of cognitive function. This article is protected by copyright. All rights reserved. |
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Country | Count | As % |
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United States | 2 | 40% |
Nigeria | 1 | 20% |
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Readers by professional status | Count | As % |
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Researcher | 11 | 14% |
Student > Master | 10 | 13% |
Other | 7 | 9% |
Student > Doctoral Student | 5 | 6% |
Other | 12 | 16% |
Unknown | 21 | 27% |
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Agricultural and Biological Sciences | 3 | 4% |
Other | 10 | 13% |
Unknown | 27 | 35% |