title: Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice.
abstract: BACKGROUND
  We hypothesized that isoflurane has a greater potency to induce neurodegeneration than sevoflurane in the developing brains of neonatal mice based on our previous studies in cell culture.
  
  
  METHODS
  We treated 7-day-old mice with either 0.75% isoflurane or 1.1% sevoflurane ( approximately 0.5 minimum alveolar concentration) for 6 h and then obtained blood and brain samples at 2 h after the anesthesia treatment for determination of neuroapoptosis in different brain regions and the neurodegenerative biomarker S100beta in the blood. The mechanisms of neurodegeneration induced by isoflurane or sevoflurane were also compared by determining protein expressions of the cell cycle and apoptosis-related proteins. In separate groups, memory and learning ability were evaluated through the use of Morris Water Maze testing in mice at postnatal day 42 after anesthesia treatment at postnatal day 7.
  
  
  RESULTS
  Isoflurane but not sevoflurane significantly increased the neurodegenerative biomarker S100beta in the blood. Isoflurane treatments significantly increased apoptosis indicated by the activation of caspase-3 and elevation of poly-(ADP-ribose) polymerase in different brain regions. An equipotent exposure of sevoflurane tended to increase apoptosis in hippocampal and cortex areas but was significantly less potent than isoflurane. Neither isoflurane nor sevoflurane significantly changed protein levels of glyceraldehyde-3-phosphate dehydrogenase, beta-site amyloid beta-precursor protein-cleaving enzyme, and cell cycle regulatory proteins (CDK4, cyclin D1). Isoflurane and sevoflurane at the selected exposures did not significantly alter memory and learning ability.
  
  
  CONCLUSIONS
  At equipotent exposures, isoflurane has a greater potency than sevoflurane to cause neurodegeneration in the developing brains of neonatal mice.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Liang
authors.forename: Christopher
authors.initials: C
authors.lastname: Ward
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Baosheng
authors.initials: B
authors.lastname: Huang
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wei
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology*; D005260:Female; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D009414:Nerve Growth Factors / Q000097:blood; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D000077149:Sevoflurane
chemical_list: D015415:Biomarkers; D008738:Methyl Ethers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000077149:Sevoflurane; D007530:Isoflurane
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