title: Modulation of murine Alzheimer pathogenesis and behavior by surgery.
abstract: OBJECTIVE
  Previous research suggests that a link between anesthetic exposure and Alzheimer disease exists. Because anesthetics are rarely given alone, we ask whether addition of surgery further modulates Alzheimer disease.
  
  
  BACKGROUND
  Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces cognitive decline in both older wild-type (WT) mice and rats, and the addition of surgery produces transient decline in young, adult WT mice. Because neuroinflammation has been implicated and occurs early in Alzheimer disease, we hypothesized that the neuroinflammatory stress associated with surgery would accelerate the progression of Alzheimer disease.
  
  
  METHODS
  Cecal ligation and excision were performed on presymptomatic 5- to 11-month-old triple-transgenic Alzheimer disease (3×TgAD) and C57BL/6 WT mice under desflurane anesthesia. Surgery animals were compared with aged-matched 3×TgAD and WT mice exposed to air or desflurane alone. Cognitive function was assessed via Morris water maze at 2 and 13 weeks postoperatively. Amyloid and tau pathology and inflammation and synaptic markers were quantified with immunohistochemistry, Luminex assay, enzyme-linked immunosorbent assay, or Western blot assays.
  
  
  RESULTS
  A significant cognitive impairment in 3×TgAD mice that underwent surgery compared with air or desflurane controls persisted to at least 14 weeks after surgery. Microglial activation, amyloidopathy, and tauopathy were enhanced by surgery as compared with desflurane alone. No differences between surgery, anesthetic, or air controls were detected in WT mice
  
  
  CONCLUSIONS
  Surgery causes a durable increment in Alzheimer pathogenesis, primarily through a transient activation of neuroinflammation.
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Junxia X
authors.initials: JX
authors.lastname: Tang
authors.forename: Feras
authors.initials: F
authors.lastname: Mardini
authors.forename: Luke S
authors.initials: LS
authors.lastname: Janik
authors.forename: Sean T
authors.initials: ST
authors.lastname: Garrity
authors.forename: Rosie Q
authors.initials: RQ
authors.lastname: Li
authors.forename: Gulnaz
authors.initials: G
authors.lastname: Bachlani
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D002432:Cecum / Q000601:surgery; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011183:Postoperative Complications / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D013514:Surgical Procedures, Operative
chemical_list: D015415:Biomarkers