title: Biphasic change of progenitor proliferation in dentate gyrus after single dose of isoflurane in young adult rats.
abstract: BACKGROUND
  Isoflurane exposure causes improvement in long-term neurocognitive function in young adult rats; this is associated with an increase in dentate gyrus (DG) progenitor proliferation 4 days after anesthesia. However, the number of new neurons that were born from cells that incorporated bromodeoxyuridine (BrdU) 4 days after anesthesia is not affected by anesthesia. We tested the hypothesis that progenitor proliferation continues to increase past 4 days, which would imply the possibility that the number of new neurons after anesthesia could be increased if BrdU labeling occurred at a later time point.
  
  
  METHODS
  BrdU was injected at 0, 1, 2, 4, 9, 16 days after 4 hours of isoflurane exposure to 60-day old rats. Brains were harvested 2 hours later, immunohistochemically stained, and the number of BrdU+ cells in the DG was assessed microscopically.
  
  
  RESULTS
  After 4 hours of exposure to isoflurane in 60-day old rats, the number of BrdU+ cells decreased on days 0 to 2, then increased on day 4 significantly, and regressed toward the control level on days 9 and 16.
  
  
  CONCLUSIONS
  Anesthesia-induced progenitor proliferation in the DG was not sustained 9 days after anesthesia. We interpret these results to signify that an anesthetic effect on neurogenesis likely does not play a critical role in the previously observed isoflurane-induced long-term improvement in neurocognitive function in 60-day old rats and that the transient increase in progenitor proliferation serves to replenish the pool of neural stem cells. The mechanism of anesthesia-induced improvement in cognition of young adult rats remains elusive.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143-0542, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.forename: Tiffany S
authors.initials: TS
authors.lastname: Moon
authors.forename: Greg
authors.initials: G
authors.lastname: Stratmann
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Sall
mesh_terms: D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D051381:Rats; D018401:Sample Size
chemical_list: D018685:Anesthetics, Inhalation; D000963:Antimetabolites; D007530:Isoflurane; D001973:Bromodeoxyuridine