title: Peripheral orthopaedic surgery down-regulates hippocampal brain-derived neurotrophic factor and impairs remote memory in mouse.
abstract: Peripheral orthopaedic surgery induces a profound inflammatory response. This includes a substantial increase in cytokines and, especially, in the level of interleukin (IL)-1β in the hippocampus, which has been shown to impair hippocampal-dependent memory in mice. We have employed two tests of contextual remote memory to demonstrate that the inflammatory response to surgical insult in mice also results in impairment of remote memory associated with prefrontal cortex (PFC). We have also found that, under the conditions presented in the social interaction test, peripheral orthopaedic surgery does not increase anxiety-like behaviour in our animal model. Although such surgery induces an increase in the level of IL-1β in the hippocampus, it fails to do so in the PFC. Peripheral orthopaedic surgery also results in a reduction in the level of hippocampal brain-derived neurotrophic factor (BDNF) and this may contribute, in part, to the memory impairment found after such surgery. Our data suggest that a reduction in the level of hippocampal BDNF and an increase in the level of hippocampal IL-1β following surgery may affect the transference of fear memory in the mouse brain.
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, London SW10 9NH, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Fidalgo
authors.forename: M
authors.initials: M
authors.lastname: Cibelli
authors.forename: J P M
authors.initials: JP
authors.lastname: White
authors.forename: I
authors.initials: I
authors.lastname: Nagy
authors.forename: F
authors.initials: F
authors.lastname: Noormohamed
authors.forename: L
authors.initials: L
authors.lastname: Benzonana
authors.forename: M
authors.initials: M
authors.lastname: Maze
authors.forename: D
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015536:Down-Regulation; D006624:Hippocampus / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011184:Postoperative Period
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta