title: Systemic inflammation enhances surgery-induced cognitive dysfunction in mice.
abstract: The activation of the immune system, by either lipopolysaccharide (LPS) administration or surgical trauma, has been shown to be capable of affecting hippocampal function, causing memory impairment. Here, we examined the extent to which LPS-induced infection may aggravate impairment of memory function following orthopaedic surgery. Hippocampal memory function impairment was assessed using fear-conditioning tasks, while IL-1β levels in plasma and hippocampus were measured using ELISA. LPS-induced inflammation disrupted hippocampal memory consolidation as evidenced by reduced contextual freezing time exhibited by infected mice. Likewise, surgery caused hippocampal-dependent memory impairment, which was associated with increased levels of IL-1β both in plasma and hippocampus. However, a sub-pyrogenic dose of LPS alone failed to impair memory function. This dose of LPS, when administered prior to surgery, exacerbated surgery-induced cognitive dysfunction as evidenced by further reduction of contextual freezing time. Also, it caused a concomitant additional increase in the levels of IL-1β in both plasma and hippocampus of those animals. Our data suggest that sub-clinical infection may sensitise the immune system augmenting the severity of post-operative cognitive dysfunction.
authors.affiliation: Anaesthesia, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Chelsea and Westminster Hospital, Imperial College School of Medicine, 369 Fulham Road, SW10 9NH London, United Kingdom.
authors.forename: António Rei
authors.initials: AR
authors.lastname: Fidalgo
authors.forename: Mario
authors.initials: M
authors.lastname: Cibelli
authors.forename: John P M
authors.initials: JP
authors.lastname: White
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000502:physiology*; D019637:Orthopedic Procedures / Q000009:adverse effects; D011183:Postoperative Complications / Q000276:immunology* / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides