title: Neuroprotective effects of propofol in a model of ischemic cortical cell cultures: role of glutamate and its transporters.
abstract: BACKGROUND
  During cerebral ischemia, excess of glutamate release and dysfunction of its high affinity transport induce an accumulation of extracellular glutamate, which plays an important role in neuronal death. The authors studied the relationship among propofol neuroprotection, glutamate extracellular concentrations, and glutamate transporter activity in a model of ischemic cortical cell cultures.
  
  
  METHODS
  Thirteen-day-old primary cortical neuronal-glial cultures were exposed to a 90-min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber, followed by reoxygenation. Propofol was added only during the OGD period, and its effect was compared to that of the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801). Twenty-four hours after the injury, cell death was quantified by lactate dehydrogenase release and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Extracellular concentrations of glutamate in culture supernatants and glutamate uptake were performed at the end of OGD period by high-performance liquid chromatography and incorporation of l-[3H]glutamate into cells, respectively.
  
  
  RESULTS
  At clinically relevant concentrations (0.05-10 microm), propofol offered protection equivalent to that of MK-801. It significantly reduced lactate dehydrogenase release and increased the reduction of MTT. At the end of the ischemic injury, propofol was able to reverse the OGD-induced increase in glutamate extracellular concentrations and decrease of glutamate uptake. The inhibition of the glial GLT1 transporter by 3-methyl-glutamate did not further modify the effect of propofol on glutamate uptake, suggesting that GLT1 was not the major target of propofol.
  
  
  CONCLUSIONS
  Propofol showed a neuroprotective effect in this in vitro model of OGD, which was apparently mediated by a GLT1-independent restoration of the glutamate uptake impaired during the injury.
authors.affiliation: Department of Anesthesiology, Centre Hospitalier Universitaire Timone, France.
authors.forename: Lionel J
authors.initials: LJ
authors.lastname: Velly
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Guillet
authors.forename: Frederique M
authors.initials: FM
authors.lastname: Masmejean
authors.forename: André L
authors.initials: AL
authors.lastname: Nieoullon
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Bruder
authors.forename: François M
authors.initials: FM
authors.lastname: Gouin
authors.forename: Pascale M
authors.initials: PM
authors.lastname: Pisano
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D005947:Glucose / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D010100:Oxygen / Q000502:physiology; D011247:Pregnancy; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D027322:Amino Acid Transport System X-AG; D000596:Amino Acids; D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D005732:Gangliosides; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D018698:Glutamic Acid; C016481:trisialoganglioside GT1; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D005947:Glucose; D010100:Oxygen; D015742:Propofol