Noninvasive assessment of the brain redox status after transient middle cerebral artery occlusion using Overhauser-enhanced magnetic resonance imaging.
Oxidative stress has been implicated in the cell death that occurs after ischemia-reperfusion of the brain, which causes the production of reactive oxygen species and a decrease in antioxidants, leading to mitochondrial dysfunction. However, the invasive methods used to collect much of this evidence are themselves stress inducing, which could skew the results. In this study, we aimed at demonstrating brain redox alterations after ischemia-reperfusion noninvasively, using Overhauser-enhanced magnetic resonance imaging. The reduction rate of 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-L-oxyl (methoxycarbonyl-PROXYL), a redox-sensitive contrast agent, was used as an index of the redox status in vivo. No changes were observed in the antioxidant concentration, the mitochondrial complex activity, or in the redox status image intensity after 3 h of reperfusion, following transient middle cerebral artery occlusion; however, after 24 h of reperfusion, the methoxycarbonyl-PROXYL reduction rate, calculated from continuous images, had decreased significantly. Concordantly, biochemical assays showed that the concentration of ascorbic acid in the ischemic hemisphere and the activity of mitochondrial complex II had also decreased. Thus, the noninvasive imaging of the brain redox alterations faithfully reflected changes in antioxidant levels and in mitochondrial complex II activity after ischemia-reperfusion.
Yamato
Mayumi
M
Department of REDOX Medicinal Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. yamato68@redoxnavi.med.kyushu-u.ac.jp
Shiba
Takeshi
T
Yamada
Ken-ichi
K
Watanabe
Toshiaki
T
Utsumi
Hideo
H
D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001205:Ascorbic Acid / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D003287:Contrast Media; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D024101:Mitochondrial Proteins / Q000032:analysis; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013997:Time Factors
D000975:Antioxidants; D003287:Contrast Media; D024101:Mitochondrial Proteins; D001205:Ascorbic Acid