title: Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia.
abstract: BACKGROUND
  Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.
  
  
  METHODS
  Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.
  
  
  RESULTS
  Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.
  
  
  CONCLUSIONS
  Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.|School of Mental Health and Neuroscience; School of Oncology and Developmental Biology, Maastricht University, and European Graduate School of Neuroscience (EURON), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.|Department of Pediatric Cardiology and Intensive Care Medicine with Neonatology, University Hospital, Georg-August-University, Robert-Koch-Str. 40, D 37099, Göttingen, Germany. matthias.seehase@med.uni-goettingen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Seehase
authors.affiliation: Department of Clinical Physics, Maasstad Hospital, Postbus 9100, 3007 AC, Rotterdam, The Netherlands. jennekensw@maasstadziekenhuis.nl.
authors.forename: Ward
authors.initials: W
authors.lastname: Jennekens
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. alexzwanenburg@gmail.com.|Department of Biomedical Technology, Maastricht University, Faculty of Health, Medicine and Life Sciences, School of Cardiovascular Diseases, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. alexzwanenburg@gmail.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Zwanenburg
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. P.Andriessen@mmc.nl.|Department of Paediatrics, Máxima Medical Center, De Run 4600, 5504 DB, Veldhoven, The Netherlands. P.Andriessen@mmc.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: Andriessen
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. j.collins@maastrichtuniversity.nl.|School of Mental Health and Neuroscience; School of Oncology and Developmental Biology, Maastricht University, and European Graduate School of Neuroscience (EURON), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. j.collins@maastrichtuniversity.nl.|Regenerative Medicine Program, Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute, 725 Parkdale Ave, Ottawa ON K1Y 4E9, Ontario, Canada. j.collins@maastrichtuniversity.nl.
authors.forename: Jennifer Jp
authors.initials: JJ
authors.lastname: Collins
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. e.kuypers@maastrichtuniversity.nl.|School of Mental Health and Neuroscience; School of Oncology and Developmental Biology, Maastricht University, and European Graduate School of Neuroscience (EURON), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. e.kuypers@maastrichtuniversity.nl.
authors.forename: Elke
authors.initials: E
authors.lastname: Kuypers
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. luc.zimmermann@mumc.nl.
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Zimmermann
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Faculty of Health, Medicine and Life Sciences, School of Mental Health and Neuroscience, Maastricht University, and European Graduate School of Neuroscience (EURON), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. jsh.vles@mumc.nl.
authors.forename: Johan Sh
authors.initials: JSh
authors.lastname: Vles
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. danilo.gavilanes@mumc.nl.
authors.forename: Antonio Wd
authors.initials: AW
authors.lastname: Gavilanes
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. b.kramer@mumc.nl.|School of Mental Health and Neuroscience; School of Oncology and Developmental Biology, Maastricht University, and European Graduate School of Neuroscience (EURON), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. b.kramer@mumc.nl.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
keywords: Asphyxia; Lamb; Neonatal resuscitation; Neuroprotection; Preterm; Propofol