title: Neutrophil gelatinase-associated lipocalin and microglial activity are associated with distinct postoperative behavioral changes in rats.
abstract: Neutrophil gelatinase-associated lipocalin (NGAL) has recently gained interest as a marker for neuroinflammation and associated behavioral dysfunction. We aimed to explore the link between NGAL and behavior in a rat model of postoperative cognitive dysfunction (POCD). Material collected in two previous studies on POCD was analyzed and associated with outcomes for exploratory behavior and spatial learning. Plasma and hippocampal NGAL and microglial activity were analyzed. Pearson's correlations and backward linear regression were performed to study the associations between behavioral parameters, NGAL concentrations, and microglial activity. Plasma and hippocampal NGAL were increased following surgery. Plasma NGAL was associated with impaired spatial learning only, microglial activity was associated with exploratory behavior only, while hippocampal NGAL was associated with both behavioral aspects. Spatial learning was best predicted by a model containing plasma NGAL concentrations and hippocampal microglial activity. NGAL may serve as a sensitive marker in connecting the peripheral inflammatory state to POCD, while postoperative changes in exploratory behavior are better reflected by hippocampal neuroinflammation. These findings warrant further exploration in the role of NGAL in development of postoperative behavioral deficits.
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands. Electronic address: l.gouweleeuw@rug.nl.
authors.forename: Leonie
authors.initials: L
authors.lastname: Gouweleeuw
authors.affiliation: 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.forename: Iris B
authors.initials: IB
authors.lastname: Hovens
authors.affiliation: Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. Electronic address: b.l.van.leeuwen@umcg.nl.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: van Leeuwen
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands. Electronic address: r.g.schoemaker@umcg.nl.
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D011183:Postoperative Complications / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: Behavior; Microglia; Neuroinflammation; Neutrophil gelatinase-associated lipocalin; Postoperative cognitive dysfunction