Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection.
Significant amounts of oxygen free radicals (oxidants) are generated during cerebral ischemia/reperfusion, and oxidative stress plays an important role in brain damage after stroke. In addition to oxidizing macromolecules, leading to cell injury, oxidants are also involved in cell death/survival signal pathways and cause mitochondrial dysfunction. Experimental data from laboratory animals that either overexpress (transgenic) or are deficient in (knock-out) antioxidant proteins, mainly superoxide dismutase, have provided strong evidence of the role of oxidative stress in ischemic brain damage. In addition to mitochondria, recent reports demonstrate that NADPH oxidase (NOX), an important pro-oxidant enzyme, is also involved in the generation of oxidants in the brain after stroke. Inhibition of NOX is neuroprotective against cerebral ischemia. We propose that superoxide dismutase and NOX activity in the brain is a major determinant for ischemic damage/repair and that these major anti- and pro-oxidant enzymes are potential endogenous molecular targets for stroke therapy.
Chen
Hai
H
Departments of Neurosurgery and Neurology and Neurological Sciences and Program in Neurosciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305-5487, USA.
Yoshioka
Hideyuki
H
Kim
Gab Seok
GS
Jung
Joo Eun
JE
Okami
Nobuya
N
Sakata
Hiroyuki
H
Maier
Carolina M
CM
Narasimhan
Purnima
P
Goeders
Christina E
CE
Chan
Pak H
PH
D000818:Animals; D016923:Cell Death; D019610:Cytoprotection; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism*
D016877:Oxidants; D013482:Superoxide Dismutase; D019255:NADPH Oxidases
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