Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain

C. Creeley, K. Dikranian, G. Dissen, L. Martin, J. Olney, A. Brambrink

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

BackgroundExposure of the fetal or neonatal non-human primate (NHP) brain to isoflurane or ketamine for 5 h causes widespread apoptotic degeneration of neurones, and exposure to isoflurane also causes apoptotic degeneration of oligodendrocytes (OLs). The present study explored the apoptogenic potential of propofol in the fetal and neonatal NHP brain.MethodFetal rhesus macaques at gestational age 120 days were exposed in utero, or postnatal day 6 rhesus neonates were exposed directly for 5 h to propofol anaesthesia (n=4 fetuses; and n=4 neonates) or to no anaesthesia (n=4 fetuses; n=5 neonates), and the brains were systematically evaluated 3 h later for evidence of apoptotic degeneration of neurones or glia.ResultsExposure of fetal or neonatal NHP brain to propofol caused a significant increase in apoptosis of neurones, and of OLs at a stage when OLs were just beginning to myelinate axons. Apoptotic degeneration affected similar brain regions but to a lesser extent than we previously described after isoflurane. The number of OLs affected by propofol was approximately equal to the number of neurones affected at both developmental ages. In the fetus, neuroapoptosis affected particularly subcortical and caudal regions, while in the neonate injury involved neocortical regions in a distinct laminar pattern and caudal brain regions were less affected.ConclusionsPropofol anaesthesia for 5 h caused death of neurones and OLs in both the fetal and neonatal NHP brain. OLs become vulnerable to the apoptogenic action of propofol when they are beginning to achieve myelination competence.

Original languageEnglish (US)
Pages (from-to)i29-i38
JournalBritish journal of anaesthesia
Volume110
Issue numberSUPPL.1
DOIs
StatePublished - Jun 2013

Keywords

  • anaesthetics i.v., propofol
  • developing brain
  • neurones
  • non-human primates
  • oligodendroglia
  • toxicity

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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