title: Neurobehavioural abnormalities induced by repeated exposure of neonatal rats to sevoflurane can be aggravated by social isolation and enrichment deprivation initiated after exposure to the anaesthetic.
abstract: BACKGROUND
  We tested the hypothesis that developmental effects of repeated neonatal exposure to sevoflurane in rats are exacerbated by stressful experiences received later in life.
  
  
  METHODS
  Sprague-Dawley male rats received sequential exposures to 3% sevoflurane for two h on postnatal days (P) six, seven, and eight. After weaning at P21, rats were housed either in pairs in an enriched environment (EE) or singly in an enrichment-deprived environment (an adverse environment, AE). The hippocampal concentrations of brain-derived neurotrophic factor (BDNF), and synaptic markers were assessed at P8 and P53. The dentate gyrus neural progenitor proliferation was evaluated at P11 and P53 after administration of bromodeoyuridine (BrdU) at P8 to P10 and at P22 to P27, respectively. Neurobehavioural evaluations were performed at P49 to P53.
  
  
  RESULTS
  Repeated sevoflurane exposure acutely reduced concentrations of BDNF, synaptic markers and neural progenitor proliferation. The sevoflurane group housed in the AE conditions (sevoflurane+AE) had decreased concentrations of BDNF and synaptic markers, and survival of new granule cells and impaired cognitive function compared with the control+AE, control+EE, and sevoflurane+EE groups. The neurobehavioural parameters in the sevoflurane+EE and control+EE groups were similar.
  
  
  CONCLUSIONS
  Neurocognitive abnormalities induced by repeated neonatal exposure to sevoflurane can be aggravated by stressful conditions such as social isolation and enrichment deprivation.
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: M H
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Q S
authors.initials: QS
authors.lastname: Zhao
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: M
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Qiu
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, China Jiangsu Province Key Laboratory of Anaesthesia and Analgesia Application Technology, Xuzhou, China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anaesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Y G
authors.initials: YG
authors.lastname: Peng
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, China Jiangsu Province Key Laboratory of Anaesthesia and Analgesia Application Technology, Xuzhou, China yjyangjj@126.com amartynyuk@anest.ufl.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anaesthesiology, University of Florida College of Medicine, Gainesville, FL, USA The McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA yjyangjj@126.com amartynyuk@anest.ufl.edu.
authors.forename: A E
authors.initials: AE
authors.lastname: Martynyuk
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D012931:Social Environment; D012934:Social Isolation / Q000523:psychology*
chemical_list: D018685:Anesthetics, Inhalation; D019208:Brain-Derived Neurotrophic Factor; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: brain-derived neurotrophic factor; cognition; environment; rats; sevoflurane; social isolation