Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics.
Oxygen-centered free radicals cause brain injury associated with trauma and stroke. These reactive oxygen species may be detoxified by endogenous antioxidants, but cell death occurs after antioxidants become depleted. General anesthetics penetrate into brain parenchyma, where they may abrogate oxidative injury to neurons by several mechanisms that prevent the initiation of free radical chain reactions or terminate the propagation of highly reactive radicals. First, general anesthetics may inhibit free radical generation because these drugs slow cerebral utilization of oxygen and glucose, inhibit oxidative metabolism in neutrophils, and prevent redox changes in hemoglobin. Second, antioxidant anesthetics, such as thiopental and propofol, directly scavenge reactive oxygen species and inhibit lipid peroxidation. Finally, anesthetics may prevent the elevation of extracellular glutamate concentration and inhibit the activation of excitatory glutamatergic receptors that augment oxidative stress after ischemia.
Wilson
John X
JX
Department of Physiology, University of Western Ontario, London, Ontario, Canada.
Gelb
Adrian W
AW
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism; D016923:Cell Death; D005609:Free Radicals / Q000378:metabolism / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism; D020521:Stroke / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism
D000777:Anesthetics; D000975:Antioxidants; D005609:Free Radicals; D005971:Glutamates; D018696:Neuroprotective Agents