Isoflurane and propofol block neurotoxicity caused by MK-801 in the rat posterior cingulate/retrosplenial cortex.
In acute brain injury syndromes, the potent N-methyl-D-aspartate (NMDA) antagonist, MK-801, can prevent neuronal degeneration, and the general anesthetics, isoflurane and propofol, may also provide neuroprotective benefits. An obstacle to the use of NMDA antagonists for neuroprotective purposes is that they can cause a neurotoxic vacuole reaction in cerebrocortical neurons. This study demonstrates the ability of isoflurane and propofol to prevent the neurotoxic vacuole reaction induced by MK-801. Low sedative doses of inhaled isoflurane (1%) or intravenous (i.v.) propofol (7.5 mg/kg/h) were as effective as higher general anesthetic doses. Thus, in the clinical management of acute brain injury conditions such as stroke and brain trauma, administration of one of these anesthetic agents together with an NMDA antagonist may be an excellent formula for obtaining optimal neuroprotection while eliminating serious side effects.
Jevtović-Todorović
V
V
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kirby
C O
CO
Olney
J W
JW
D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001925:Brain Damage, Chronic / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000473:pathology; D006213:Hallucinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007530:Isoflurane / Q000494:pharmacology / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000187:drug effects; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007530:Isoflurane; D015742:Propofol