Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity.
The effect of propofol on the toxicity induced by glutamate (GLU), N-methyl-D-aspartate (NMDA), kainate (KA), and amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was investigated on cultured fetal rat hippocampal neurons. The degree of neuronal injury was quantified by measuring the release of the neuron-specific enolase (NSE) into the culture media. The toxicity induced by brief exposure to GLU (10(-4) M) or to NMDA (10(-4) M) was significantly reduced by propofol, whereas that elicited by KA, AMPA (10(-4) M), or long GLU exposure was unaffected. In conclusion, high concentrations of propofol significantly attenuate NMDA receptor-mediated glutamate neurotoxicity in vitro. Further studies are needed to confirm this beneficial effect in vivo and to evaluate propofol as a neuroprotective anesthetic agent in pathologies involving glutamate release and NMDA-mediated toxicity.
Hans
P
P
University Department of Anesthesia and Intensive Care, University of Liège, Belgium.
Bonhomme
V
V
Collette
J
J
Albert
A
A
Moonen
G
G
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005333:Fetus; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007608:Kainic Acid / Q000633:toxicity; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010751:Phosphopyruvate Hydratase / Q000032:analysis / Q000378:metabolism; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid; D015742:Propofol