Journal
BRAIN RESEARCH
Volume 1305, Issue -, Pages 158-167Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2009.09.061
Keywords
Allopurinol; Electrochemical sensor; Forebrain ischemia; Reperfusion; Superoxide anion radical; Xanthine oxidase inhibitor
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Funding
- Ministry of Education, Science, Sports and Culture of Japan [19791328]
- Ministry of Health, Labor and Welfare of Japan [H18-trans-general-003]
- Grants-in-Aid for Scientific Research [19791328] Funding Source: KAKEN
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We recently reported that excessive superoxide anion radical (O-2(-center dot)) was generated in the jugular vein during reperfusion in rats with forebrain ischemia/reperfusion using a novel electrochemical sensor and excessive O-2(-center dot) generation was associated with oxidative stress, early inflammation, and endothelial injury. However, the source of O-2(-center dot) was still unclear. Therefore, we used allopurinol, a potent inhibitor of xanthine oxidase (XO), to clarify the source of O-2(-center dot) generated in rats with forebrain ischemia/reperfusion. The increased O-2(-center dot) current and the quantified partial value of electricity (Q), which was calculated by the integration of the current, were significantly attenuated after reperfusion by pretreatment with allopurinol. Malondialdehyde (MDA) in the brain and plasma, high-mobility group box 1 (HMGB1) in plasma, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma were significantly attenuated in rats pretreated with allopurinol with dose-dependency in comparison to those in control rats. There were significant correlations between total Q and MDA, HMGB, or ICAM-1 in the brain and plasma. Allopurinol pretreatment suppressed O-2(-center dot) generation in the brain-perfused blood in the jugular vein, and oxidative stress, early inflammation, and endothelial injury in the acute phase of forebrain ischemia/reperfusion. Thus, XO is one of the major sources of O-2(-)- in blood after reperfusion in rats with forebrain ischemia/reperfusion. @ 2009 Elsevier B.V. All rights reserved.
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