title: Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats.
abstract: BACKGROUND
  Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats. We tested the hypothesis that isoflurane impairs neurogenesis and hippocampal function in aged rats.
  
  
  METHODS
  Isoflurane was administered to 16-month-old rats at one minimum alveolar concentration for 4 h. FluoroJade staining was performed to assess brain cell death 16 h after isoflurane administration. Dentate gyrus progenitor proliferation was assessed by bromodeoxyuridine injection 4 days after anesthesia and quantification of bromodeoxyuridine+ cells 12 h later. Neuronal differentiation was studied by determining colocalization of bromodeoxyuridine with the immature neuronal marker NeuroD 5 days after anesthesia. New neuronal survival was assessed by quantifying cells coexpressing bromodeoxyuridine and the mature neuronal marker NeuN 5 weeks after anesthesia. Four months after anesthesia, associative learning was assessed by fear conditioning. Spatial reference memory acquisition and retention was tested in the Morris Water Maze.
  
  
  RESULTS
  Cell death was sporadic and not different between groups. We did not detect any differences in hippocampal progenitor proliferation, neuronal differentiation, new neuronal survival, or in any of the tests of long-term hippocampal function.
  
  
  CONCLUSIONS
  In aged rats, isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome.
authors.affiliation: Department of Anesthesia, University of California-San Francisco, 513 Parnassus Ave., San Francisco, California 94143, USA. stratman@anesthesia.ucsf.edu
authors.forename: Greg
authors.initials: G
authors.lastname: Stratmann
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Sall
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bell
authors.forename: Rehan S
authors.initials: RS
authors.lastname: Alvi
authors.forename: Laura d V
authors.initials: Ld
authors.lastname: May
authors.forename: Ban
authors.initials: B
authors.lastname: Ku
authors.forename: Mitra
authors.initials: M
authors.lastname: Dowlatshahi
authors.forename: Ran
authors.initials: R
authors.lastname: Dai
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bickler
authors.forename: Isobel
authors.initials: I
authors.lastname: Russell
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lee
authors.forename: Margit W
authors.initials: MW
authors.lastname: Hrubos
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chiu
mesh_terms: D000375:Aging / Q000502:physiology / Q000523:psychology; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D007150:Immunohistochemistry; D007530:Isoflurane / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane