Oxidants, antioxidants and the ischemic brain.
Despite numerous defenses, the brain is vulnerable to oxidative stress resulting from ischemia/reperfusion. Excitotoxic stimulation of superoxide and nitric oxide production leads to formation of highly reactive products, including peroxynitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Use of transgenic mutants and selective pharmacological antioxidants has greatly increased understanding of the complex interplay between substrate deprivation and ischemic outcome. Recent evidence that reactive oxygen/nitrogen species play a critical role in initiation of apoptosis, mitochondrial permeability transition and poly(ADP-ribose) polymerase activation provides additional mechanisms for oxidative damage and new targets for post-ischemic therapeutic intervention. Because oxidative stress involves multiple post-ischemic cascades leading to cell death, effective prevention/treatment of ischemic brain injury is likely to require intervention at multiple effect sites.
Warner
David S
DS
Department of Anesthesiology, The Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, NC 27710, USA. warne002@mc.duke.edu
Sheng
Huaxin
H
Batinić-Haberle
Ines
I
D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019097:Spin Trapping; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D002614:Chelating Agents; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016877:Oxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D011065:Poly(ADP-ribose) Polymerases