title: General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt.
abstract: BACKGROUND
  The developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.
  
  
  METHODS
  Wistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.
  
  
  RESULTS
  There was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.
  
  
  CONCLUSIONS
  I.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt.
authors.affiliation: Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: C-M
authors.initials: CM
authors.lastname: Lacoh
authors.forename: T
authors.initials: T
authors.lastname: Bodogan
authors.forename: K
authors.initials: K
authors.lastname: Kaila
authors.forename: H
authors.initials: H
authors.lastname: Fiumelli
authors.forename: L
authors.initials: L
authors.lastname: Vutskits
mesh_terms: D000375:Aging / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D000096922:K Cl- Cotransporters
chemical_list: D018686:Anesthetics, Intravenous; D007649:Ketamine; D008874:Midazolam; D015742:Propofol; D012333:RNA, Messenger; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: anaesthesia, paediatric; brain, GABA; neonates; toxicity, neurotoxicity