title: Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats.
abstract: BACKGROUND
  Patients with postoperative cognitive dysfunction have poor outcomes. Neuroinflammation may be the underlying pathophysiology for this dysfunction. We determined whether proinflammatory cytokines affect the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors to the plasma membrane, a fundamental biochemical process for learning and memory.
  
  
  METHODS
  Four-month-old male Fischer 344 rats were subjected to right carotid exposure under isoflurane anesthesia. Some rats received intravenous lidocaine infusion during anesthesia. Rats were tested two weeks later by Barnes maze. The hippocampus was harvested six hours after the surgery for western blotting of interleukin (IL)-1β or IL-6. Hippocampal slices were prepared from control rats or rats subjected to surgery two weeks previously. They were incubated with tetraethylammonium, an agent that can induce long term potentiation, for determining the trafficking of GluR1, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit.
  
  
  RESULTS
  Surgery or anesthesia increased the time to identify the target box during the Barnes maze test training sessions and one day after the training sessions. Surgery also prolonged the time to identify the target box eight days after the training sessions. Surgery increased IL-1β and IL-6 in the hippocampus. The tetraethylammonium-induced GluR1 phosphorylation and trafficking were abolished in the hippocampal slices of rats after surgery. These surgical effects were partly inhibited by lidocaine. The incubation of control hippocampal slices with IL-1β and IL-6 abolished tetraethylammonium-induced GluR1 trafficking and phosphorylation. Lidocaine minimally affected the effects of IL-1β on GluR1 trafficking.
  
  
  CONCLUSIONS
  Our results suggest that surgery increases proinflammatory cytokines that then inhibit GluR1 trafficking, leading to learning and memory impairment.
authors.forename: Hongying
authors.initials: H
authors.lastname: Tan
authors.forename: Jiangbei
authors.initials: J
authors.lastname: Cao
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA. zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D007859:Learning Disabilities / Q000209:etiology* / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism; D011183:Postoperative Complications / Q000503:physiopathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D018091:Receptors, AMPA / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007530:Isoflurane; D008012:Lidocaine; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D019789:Tetraethylammonium