title: Isoflurane in the presence or absence of surgery increases hippocampal cytokines associated with memory deficits and responses to brain injury in rats.
abstract: Evidence from experimental animal studies convincingly argues for a role of pro-inflammatory cytokines due to surgical trauma in causing postoperative cognitive dysfunction. However, other studies have shown exposure to 2-4h of isoflurane anesthetic without surgical trauma can also impair cognitive function. We aimed to determine cytokine changes over time following isoflurane exposure in the presence and absence of surgery and examine subsequent cognitive function. Male rats were exposed to isoflurane (1.8%, 4h) with or without laparotomy or control conditions and tested in a contextual fear conditioning paradigm 8 days later. On day 9 rats were perfused, serum and hippocampal samples were collected and 24 cytokines were analysed. Groups of rats exposed as above were killed 6 or 48h after isoflurane exposure to examine early cytokine changes. Isoflurane exposure resulted in significantly less freezing in the contextual fear conditioning test (F(2,31)=6.11, P=0.006) and addition of laparotomy caused no further deficits (P>0.05). At 6h post isoflurane exposure an immunosuppressive response was observed in the serum while hippocampal cytokines were largely unchanged. These finding suggest isoflurane alone causes inflammatory changes and cognitive deficits. The addition of a laparotomy had a negligible effect. Early after isoflurane exposure changes in serum and hippocampal cytokines were divergent but by 9 days were aligned. At this time cytokines associated with memory deficits and brain injury processes were significantly elevated in serum and brain.
authors.affiliation: Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Callaway
authors.affiliation: Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Wood
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. Electronic address: trisha.jenkins@rmit.edu.au.
authors.forename: Trisha A
authors.initials: TA
authors.lastname: Jenkins
authors.affiliation: Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; Department of Cardiac Surgery, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Royse
authors.affiliation: Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Colin F
authors.initials: CF
authors.lastname: Royse
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000009:adverse effects*; D007813:Laparotomy / Q000009:adverse effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D007530:Isoflurane
keywords: Anesthetics inhalation; Cognitive; Inflammation; Isoflurane; Memory disorders; Retention disorders