Hydroxyl radical production in the cortex and striatum in a rat model of focal cerebral ischemia

Background: Increases in hydroxyl radical production have been used as evid ence of oxidative stress in cerebral ischemia/reperfusion, Ischemia can als o induce increased dopamine release from the striatum that may contribute t o hydroxyl radical formation. We have compared hydroxyl radical production in the cortex and striatum as an index of oxidative stress in a rat model o f focal cerebral ischemia with cortical infarction. Methods: Using a three vessel occlusion model of focal cerebral ischemia combined with bilateral m icrodialysis, hydroxylation of 4-hydroxybenzoate (4HB) was continuously mon itored in both hemispheres in either the lateral striatum or frontoparietal cortex. The ischemia protocol consisted of one hour equilibration, 30 min of three vessel occlusion, then release of the contralateral common carotid artery (CCA) for 2.5 h, Results: Induction of ischemia resulted in a 30-fo ld increase in dopamine release in the lateral striatum. Compared to the no nischemic striatum, the ratio of the hydroxylation product 3,4-dihydroxyben zoate (34DHB) to 4HB (trapping agent) in the ipsilateral striatum increased significantly 30 min after ischemia induction. In contrast, during the 30 min of three vessel occlusion there was no increase in the ratio in the cor tex. Following the release of the contralateral CCA, the ratio from the isc hemic cortex increased significantly compared to sham-operated animals. How ever, under all circumstances, the 34DHB/4HB ratio was greater in the stria tum than in the cortex. Conclusion: The increase in the 34DHB/4HB ratio in the lateral striatum coincides with the increased dopamine release suggesti ng a role for dopamine oxidation in the increased production of hydroxyl ra dicals. The significant increase in the ratio from the ischemic cortex comp ared to that from the sham-operated animals is consistent with increased ox idative stress induced by ischemia, However, the lower 34DHB/4HB ratio in t he cortex which does not receive dopaminergic innervation compared to the s triatum suggests a different mechanism for hydroxyl radical production. Suc h an alternate mechanism may represent a more toxic oxidative insult that c ontributes to infarction.