title: Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice.
abstract: BACKGROUND
  Problems with learning and memory are common after surgery in the elderly and are associated with high morbidity. Heat shock protein 72 (Hsp72) confers neuroprotection against acute neurologic injury. We hypothesized that overexpression of Hsp72 would prevent the development of postoperative memory loss.
  
  
  METHODS
  C57BL/6 wild-type and Hsp72 overexpressing transgenic mice were randomly allocated to the following: control, isoflurane anesthesia alone, or tibial fracture during isoflurane anesthesia. Animals were trained 24 h before surgery using a fear conditioning protocol and assessed in their training environment and in a novel context on posttreatment days 1, 3, and 7. Microglial activation was assessed by immunostaining.
  
  
  RESULTS
  Adult male C57BL/6 wild-type mice exhibited reduced memory evidenced by a decreased percentage freezing time on days 1 and 3 after anesthesia alone (58.8 ± 5, 46.5 ± 5 mean ± SEM) and after surgery (53.4 ± 6, 44.1 ± 7), compared with controls (78.8 ± 5, 63.4 ± 6; P < 0.05 and P < 0.001, respectively). Hsp72 mice showed no difference by treatment on any day. Similarly, nonhippocampal-dependent memory was significantly impaired on days 1 and 3 after surgery and day 3 after anesthesia. The genotype effect was significant on days 1 and 7. CD68-immunopositive activated microglia in the hippocampus varied modestly with subregion and time; on day 7, there was a significant treatment effect with no genotype effect, with more activated microglia after surgery in all regions.
  
  
  CONCLUSIONS
  Hsp72 overexpression is associated with prevention of postoperative hippocampal-dependent and -independent memory deficit induced by anesthesia and/or surgery. Memory deficit is not correlated with numbers of activated hippocampal microglia.
authors.affiliation: Department of Surgery and Cancer, Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London, United Kingdom.
authors.forename: Marcela P
authors.initials: MP
authors.lastname: Vizcaychipi
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000768:Anesthesia, General / Q000009:adverse effects*; D000818:Animals; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009985:Orthopedics; D011184:Postoperative Period; D011897:Random Allocation; D013997:Time Factors
chemical_list: D050884:HSP72 Heat-Shock Proteins