title: Ketamine exposure during embryogenesis inhibits cellular proliferation in rat fetal cortical neurogenic regions.
abstract: BACKGROUND
  Developmental neurotoxicity of ketamine, an N-methyl-D-aspartate receptor antagonist, must be considered due to its widespread uses for sedation/analgesia/anesthesia in pediatric and obstetric settings. Dose-dependent effects of ketamine on cellular proliferation in the neurogenic regions of rat fetal cortex [ventricular zone (VZ) and subventricular zone (SVZ)] were investigated in this in vivo study.
  
  
  METHODS
  Timed-pregnant Sprague-Dawley rats at embryonic day 17 (E17) were given with different doses of ketamine intraperitoneally (0, 1, 2, 10, 20, 40, and 100 mg/kg). Proliferating cells in the rat fetal brains were labeled by injecting 100 mg/kg of 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally. BrdU-labeled cells were detected by immunostaining methods. The numbers of BrdU-positive cells in VZ and SVZ of rat fetal cortex were employed to quantify proliferation in the developing rat cortex.
  
  
  RESULTS
  Ketamine dose-dependently reduced the number of BrdU-positive cells in VZ (P < 0.001) and SVZ (P < 0.001) of the rat fetal cortex. SVZ showed greater susceptibility to ketamine-induced reduction of proliferation in rat fetal cortex, occurring even at clinically relevant doses (2 mg/kg).
  
  
  CONCLUSIONS
  These data suggest that exposure to ketamine during embryogenesis can dose-dependently inhibit the cellular proliferation in neurogenic regions of the rat fetal cortex.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.|Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: C
authors.identifier: http://orcid.org/0000-0002-9523-9801
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Rovnaghi
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: K J S
authors.initials: KJ
authors.lastname: Anand
mesh_terms: D000778:Anesthetics, Dissociative / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology*; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D007649:Ketamine / Q000633:toxicity*; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D055495:Neurogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine
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