title: Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review.
abstract: Delirium is a frequent outcome for aged and demented patients that suffer a systemic inflammatory insult. Animal models that reconstruct these etiological processes have potential to provide a better understanding of the pathophysiology of delirium. Therefore, we systematically reviewed animal studies in which systemic inflammation was superimposed on aged or diseased animal models. In total, 77 studies were identified. Aged animals were challenged with a bacterial endotoxin in 29 studies, 25 studies superimposed surgery on aged animals, and in 6 studies a bacterial infection, Escherichia coli (E. coli), was used. Diseased animals were challenged with a bacterial endotoxin in 15 studies, two studies examined effects of the cytokine IL-1β, and one study used polyinosinic:polycytidilic acid (poly I:C). This systematic review analyzed the impact of systemic inflammation on the production of inflammatory and neurotoxic mediators in peripheral blood, cerebrospinal fluid (CSF), and on the central nervous system (CNS). Moreover, concomitant behavioral and cognitive symptoms were also evaluated. Finally, outcomes of behavioral and cognitive tests from animal studies were compared to features and symptoms present in delirious patients.
authors.affiliation: University of Groningen, University Medical Center Groningen, University Center for Geriatric Medicine, Groningen, The Netherlands. Electronic address: l.schreuder@umcg.nl.
authors.forename: Leroy
authors.initials: L
authors.lastname: Schreuder
authors.affiliation: Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: b.j.l.eggen@umcg.nl.
authors.forename: B J
authors.initials: BJ
authors.lastname: Eggen
authors.affiliation: Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Psychiatry and Psychotherapy, Section of Molecular Psychiatry, University of Freiburg, Freiburg, Germany. Electronic address: Knut.Biber@uniklinik-freiburg.de.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
authors.affiliation: Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands. Electronic address: r.g.schoemaker@umcg.nl.
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
authors.affiliation: Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: j.d.laman@umcg.nl.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: University of Groningen, University Medical Center Groningen, University Center for Geriatric Medicine, Groningen, The Netherlands. Electronic address: s.e.j.a.de.rooij@umcg.nl.
authors.forename: Sophia E
authors.initials: SE
authors.lastname: de Rooij
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003693:Delirium / Q000276:immunology / Q000523:psychology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000523:psychology*; D051379:Mice; D051381:Rats
keywords: Acute cognitive dysfunction; Aging; Astrocytes; Cytokines; Infection; LPS; Microglia; Neuroinflammation; Sickness behavior; Surgery