Extracellular Ascorbic Acid Radical formation During Cerebral Ischemia-Reperfusion Utilizing 4-Vessel Occlusion In Rats

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  • 脳虚血再灌流における細胞外アスコルビン酸ラジカルの動態

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Abstract

Background: Free radicals are thought to contribute to brain damage in ischemia-reperfusion. In the normal state, there is a balance between free radical formation and a defense mechanism, which prevents tissue injury. Ascorbic acid, widely-regarded as an important antioxidant, is highly concentrated in the central nervous system. In the present study, we demonstrate changes in extracellular ascorbic acid radical concentration in ischemia-reperfusion by employing microdialysis and electron spin resonance (ESR). Method: Using a modified Pulsinelli's 4-vessel occlusion model, ischemia was induced for 45 minutes. A microdialysis probe was inserted into the frontal cortex. Spin adducts in perfusate samples were detected by ESR. To assess the influence of radical scavengers on extracellelar ascorbic acid radicals in ischemiareperfusion, superoxide dismutase (SOD) or edaravone (3-methyl-1 -phenyl-2-pyrazolin-5-one), was administered to rats, either intravenously or by infusion into the brain parenchyma. Findings: ESR spectra from perfusate samples exhibited a stable doublet signal consistent with ascorbic acid radical. Extracellular ascorbic acid radicals were detected in the pre-ischemic (control), ischemic and post-ischemic states. The extracellular ascorbic acid radical concentration was increased by ischemia and further increased by reperfusion (n=6, p<0.05). Intravenous administration of SOD (n=6) did not decrease extracellular ascorbic acid radical formation, and treatment with edaravone intravenously (n=6) did not influence the formation after reperfusion. SOD administration into brain parenchyma (n=6) markedly decreased extracellular ascorbic acid radical formation. However, edaravone administration into brain parenchyma (n=6) did not decrease its formation. Conclusions: We detected ascorbic acid radicals in perfusates using a modified Pulsinelli's 4-vessel occlusion model by microdialysis and ESR. The concentrations of extracellular ascorbic acid radicals increased during cerebral ischemia and reperfusion of the rat brain. Intravenous administration of SOD and edaravone did not decrease ascorbic acid radical formation. However, SOD but not edaravone administration into the brain parenchyma markedly decreased extracellular ascorbic acid radical formation. The present data indicates that extracellular ascorbic acid radicals may be an additional marker for superoxide radical formation.

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