title: Effects of sevoflurane exposure during late pregnancy on brain development of offspring mice.
abstract: BACKGROUND
  Exposure to some anesthetic agents during the fetal period has been shown to induce neurodegeneration or learning deficits in animal models. Sevoflurane is one of the most prevalent general anesthetics; however, the influence of sevoflurane at a clinically relevant concentration on the developing fetal brain remains unknown.
  
  
  OBJECTIVE
  We investigated whether a single sevoflurane exposure during the fetal period would affect neuronal development and learning/memory ability in mice.
  
  
  METHODS
  Pregnant mice at gestational day 17 were anesthetized with 1.5% sevoflurane in 50% oxygen for 6 h. Mice in the control group were exposed in 50% oxygen without sevoflurane. Pups of some mice in both groups subsequently were delivered early by cesarean section and whole fetal brains were excised. The rest of the pups were delivered naturally at gestational day 20 and were maintained for 8 weeks. The mRNA expression levels of caspase-3, brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), and LIM kinase-1 (LIMK-1) were measured in fetal whole brain and 8-week-old hippocampus sections. Synaptophysin protein in adult hippocampus was assessed immunochemically. In addition, 8-week-old mice were subjected to the radial maze test.
  
  
  RESULTS
  No significant difference between sevoflurane and control groups regarding mRNA expression levels of all targets was seen, nor was there an obvious change in synaptophysin protein expression. The results of the maze test revealed that the each-day performance ratios (the rate of errors) of the sevoflurane group were not altered as compared with the control group.
  
  
  CONCLUSIONS
  These results suggest that the exposure during late pregnancy to a clinically relevant concentration of sevoflurane does not affect neuronal development and learning/memory ability of offspring mice.
authors.affiliation: Division of Anesthesiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Suehara
authors.affiliation: Department of Anesthesiology, Higashiosaka City General Hospital, Higashiosaka, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Morishita
authors.affiliation: Department of Anesthesiology, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.affiliation: Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Anesthesiology, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Maekawa
authors.affiliation: Division of Anesthesiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mizobuchi
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D054461:Lim Kinases / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D019208:Brain-Derived Neurotrophic Factor; D008738:Methyl Ethers; D000077149:Sevoflurane; C579455:BDNF protein, human; D020932:Nerve Growth Factor; D054461:Lim Kinases; D053148:Caspase 3
keywords: developing brain; fetal mouse; neurotoxicity; neurotrophin; sevoflurane; synaptophysin