Propofol and sodium thiopental protect against MK-801-induced neuronal necrosis in the posterior cingulate/retrosplenial cortex.
N-Methyl-D-aspartate (NMDA) antagonists act by an anti-excitotoxic action to provide neuroprotection against acute brain injury, but these agents can also cause toxic effects. In low doses they induce reversible neuronal injury, but in higher doses they cause irreversible degeneration of cerebrocortical neurons. GABAmimetic drugs protect against the reversible neurotoxic changes in rat brain. Here we show that two GABAmimetic anesthetic agents--propofol and sodium thiopental--protect against the irreversible neurodegenerative reaction induced by the powerful NMDA antagonist, MK-801.
Jevtovic-Todorovic
V
V
Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, P.O. Box 8054, St. Louis, MO 63110, USA. todorovv@msotes.wustl.edu
Wozniak
D F
DF
Powell
S
S
Olney
J W
JW
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013874:Thiopental / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D013874:Thiopental; D015742:Propofol