title: Inhibition of N-myc downstream-regulated gene-2 is involved in an astrocyte-specific neuroprotection induced by sevoflurane preconditioning.
abstract: BACKGROUND
  Mechanism of sevoflurane preconditioning-induced cerebral ischemic tolerance is unclear. This study investigates the role of N-myc downstream-regulated gene-2 (NDRG2) in the neuroprotection of sevoflurane preconditioning in ischemic model both in vivo and in vitro.
  
  
  METHODS
  At 2 h after sevoflurane (2%) preconditioning for 1 h, rats were subjected to middle cerebral artery occlusion for 120 min. Neurobehavioral scores (n = 10), infarct volumes (n = 10), cellular apoptosis (n = 6), and NDRG2 expression (n = 6) were determined at 24 h after reperfusion. In vitro, cultural astrocytes were exposed to oxygen-glucose deprivation for 4 h. Cellular viability, cytotoxicity, apoptosis, and NDRG2 expression (n = 6) were evaluated in the presence or absence of NDRG2-specific small interfering RNA or NDRG2 overexpression plasmid.
  
  
  RESULTS
  Sevoflurane preconditioning decreased apoptosis (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling-positive cells reduced to 31.2 ± 5.3% and cleaved Caspase-3 reduced to 1.42 ± 0.21 fold) and inhibited NDRG2 expression (1.28 ± 0.15 fold) and nuclear translocation (2.21 ± 0.29 fold) in ischemic penumbra. Similar effects were observed in cultural astrocytes exposed to oxygen-glucose deprivation. NDRG2 knockdown by small interfering RNA attenuated oxygen-glucose deprivation-induced injury (cell viability increased to 80.5 ± 4.1%; lactate dehydrogenase release reduced to 30.5 ± 4.0%) and cellular apoptosis (cleaved Caspase-3 reduced to 1.55 ± 0.21 fold; terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling-positive cells reduced to 18.2 ± 4.3%), whereas NDRG2 overexpression reversed the protective effects of sevoflurane preconditioning. All the data are presented as mean ± SD.
  
  
  CONCLUSIONS
  Sevoflurane preconditioning inhibits NDRG2 up-regulation and nuclear translocation in astrocytes to induce cerebral ischemic tolerance via antiapoptosis, which represents one new mechanism of sevoflurane preconditioning and provides a novel target for neuroprotection.
authors.affiliation: From the Department of Anesthesiology (X.L., F.W., Q.Y., Y.L., S.W., Q.W., L.X.) and Department of Neurosurgery (P.L., M.Z.), Xijing Hospital, Fourth Military Medical University, Xi'an, China; and Department of Anesthesiology, Shaanxi Provincial Maternal and Child Health Hospital, Xi'an, China (Y.L.).
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D021581:Active Transport, Cell Nucleus; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000502:physiology*; D002545:Brain Ischemia / Q000517:prevention & control; D002478:Cells, Cultured; D019194:Ischemic Preconditioning; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D000077149:Sevoflurane