title: Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory.
abstract: BACKGROUND
  In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown.
  
  
  METHODS
  Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively.
  
  
  RESULTS
  Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory.
  
  
  CONCLUSIONS
  In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.
authors.affiliation: Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Kodama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Otsubo
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Araki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yonamine
authors.forename: Kenichi
authors.initials: K
authors.lastname: Masui
authors.forename: Tomiei
authors.initials: T
authors.lastname: Kazama
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077335:Desflurane; D020287:In Situ Nick-End Labeling; D007530:Isoflurane / Q000031:analogs & derivatives / Q000633:toxicity; D008570:Memory, Short-Term / Q000187:drug effects*; D008738:Methyl Ethers / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D010100:Oxygen