Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction.
Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.
Department of Neurosurgery, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Hao
H
Liu
Masaaki
M
Uno
Keiko T
KT
Kitazato
Atsuhiko
A
Suzue
Shiji
S
Manabe
Hiroyuki
H
Yamasaki
Masayuki
M
Shono
Shinji
S
Nagahiro
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine