title: Effect of propofol in the immature rat brain on short- and long-term neurodevelopmental outcome.
abstract: BACKGROUND
  Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment.
  
  
  METHODS
  6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120.
  
  
  RESULTS
  Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point.
  
  
  CONCLUSIONS
  Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.
authors.affiliation: Department of Paediatrics I, Neonatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. tanja.karen@uk-essen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Karen
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Schlager
authors.forename: Ivo
authors.initials: I
authors.lastname: Bendix
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
authors.forename: Ralf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Christos
authors.initials: C
authors.lastname: Pantazis
authors.forename: David
authors.initials: D
authors.lastname: Enot
authors.forename: Matthias
authors.initials: M
authors.lastname: Keller
authors.forename: Thoralf
authors.initials: T
authors.lastname: Kerner
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Mueser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D007527:Isoenzymes; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D015742:Propofol