title: Anesthetic sevoflurane causes neurotoxicity differently in neonatal naïve and Alzheimer disease transgenic mice.
abstract: BACKGROUND
  Recent studies have suggested that children undergoing surgery under anesthesia could be at an increased risk for the development of learning disabilities, but whether anesthetics contribute to this learning disability is unclear. Therefore, the authors set out to assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on caspase activation, apoptosis, beta-amyloid protein levels, and neuroinflammation in the brain tissues of neonatal naïve and Alzheimer disease (AD) transgenic mice.
  
  
  METHODS
  Six-day-old naïve and AD transgenic (B6.Cg-Tg[amyloid precursor protein swe, PSEN1dE9]85Dbo/J) mice were treated with sevoflurane. The mice were killed at the end of the anesthesia, and the brain tissues were harvested and then subjected to Western blot, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction.
  
  
  RESULTS
  Herein, the authors show for the first time that sevoflurane anesthesia induced caspase activation and apoptosis, altered amyloid precursor protein processing, and increased beta-amyloid protein levels in the brain tissues of neonatal mice. Furthermore, sevoflurane anesthesia led to a greater degree of neurotoxicity in the brain tissues of the AD transgenic mice when compared with naïve mice and increased tumor necrosis factor-alpha levels in the brain tissues of only the AD transgenic mice. Finally, inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate attenuated sevoflurane-induced caspase-3 activation and beta-amyloid protein accumulation in vivo.
  
  
  CONCLUSIONS
  These results suggest that sevoflurane may induce neurotoxicity in neonatal mice. AD transgenic mice could be more vulnerable to such neurotoxicity. These findings should promote more studies to determine the potential neurotoxicity of anesthesia in animals and humans, especially in children.
authors.affiliation: Geriatric Anesthesia Research Unit, Departmentof Anesthesia, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129-2060, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control; D008738:Methyl Ethers / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D053148:Caspase 3
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