title: Isoflurane Preconditioning Promotes the  Survival and Migration of Bone Marrow  Stromal Cells.
abstract: BACKGROUND
  Preconditioning with the volatile anesthetic isoflurane exerts protective effects in animal models of ischemia. The cytoprotective effects of isoflurane are dependent on the expression of hypoxia inducible factor-1 (HIF-1), a dimeric transcription factor that mediates cellular responses to hypoxia.
  
  
  METHODS
  We investigated the effect of isoflurane preconditioning on bone marrow stromal cell (BMSC) survival and function.
  
  
  RESULTS
  Short exposures to low isoflurane concentrations promoted in vitro survival and migration of BMSCs, whereas long exposures and high doses had the opposite effect. At specific doses and times, isoflurane upregulated the expression of HIF-1α and the stromal-derived factor-1 receptor CXCR4, and induced the activation of Akt, similar to hypoxia, and the effect of isoflurane was abrogated by silencing of HIF-1α or inhibition of PI3K/Akt signaling. In vivo experiments showed that isoflurane preconditioning increased the engraftment of BMSCs into the ischemic brain and improved functional recovery in a mouse model of stroke.
  
  
  CONCLUSIONS
  Isoflurane preconditioning at specific doses and times improves the survival and function of BMSCs through the upregulation of CXCR4 via a mechanism involving HIF-1α expression and the PI3K/Akt pathway, suggesting that anesthetic preconditioning could be developed as a strategy to improve the efficiency of cell therapy.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Qi-fang
authors.initials: QF
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D007530:Isoflurane; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt