title: Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats.
abstract: BACKGROUND
  Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between these findings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis.
  
  
  METHODS
  The S-phase marker 5-bromodeoxyuridine was administered at various times before, during, and after 4 h of isoflurane given to postnatal day (P)60 and P7 rats to assess dentate gyrus progenitor proliferation, early neuronal lineage selection, and long-term survival of new granule cell neurons. Fear conditioning and spatial reference memory was tested at various intervals from 2 weeks until 8 months after anesthesia.
  
  
  RESULTS
  In P60 rats, isoflurane increased early neuronal differentiation as assessed by BrdU/NeuroD costaining, decreased progenitor proliferation for 1 day, and subsequently increased progenitor proliferation 5-10 days after anesthesia. In P7 rats, isoflurane did not induce neuronal lineage selection but decreased progenitor proliferation until at least 5 days after anesthesia. Isoflurane improved spatial reference memory of P60 rats long-term, but it caused a delayed-onset, progressive, persistent hippocampal deficit in P7 rats in fear conditioning and spatial reference memory tasks.
  
  
  CONCLUSIONS
  The authors conclude that isoflurane differentially affects both neurogenesis and long-term neurocognitive function in P60 and P7 rats. Neurogenesis might mediate the long-term neurocognitive outcome after isoflurane at different ages.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco 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: Laura D V
authors.initials: LD
authors.lastname: May
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bell
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Magnusson
authors.forename: Vinuta
authors.initials: V
authors.lastname: Rau
authors.forename: Kavel H
authors.initials: KH
authors.lastname: Visrodia
authors.forename: Rehan S
authors.initials: RS
authors.lastname: Alvi
authors.forename: Ban
authors.initials: B
authors.lastname: Ku
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lee
authors.forename: Ran
authors.initials: R
authors.lastname: Dai
mesh_terms: D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D001973:Bromodeoxyuridine; D016923:Cell Death; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects*; D007530:Isoflurane / Q000009:adverse effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D051381:Rats; D016896:Treatment Outcome
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D001973:Bromodeoxyuridine