Uric acid administration for neuroprotection in patients with acute brain ischemia

Uric acid is the end product of purine metabolism and a powerful water-soluble antioxidant and radical scavenger in humans whose generation is increased in situations of oxidative stress, such as brain ischemia. Although hyperuricemia has been related to an increased risk of cardiovascular events, the association was not found significant in many studies after adjustment for the effect of confounders. In the ischemic rat brain, the administration of uric acid results in neuroprotection and improved behavioral outcome. The severity of neurological impairment and the volume of infarction in patients with stroke have been found inversely related to the concentration of uric acid. In healthy volunteers, uric acid has been administered without untoward effects to show a conspicuous reduction of oxidative stress. We hypothesize that the administration of uric acid could be beneficial and cost effective in patients sustaining acute oxidative stress, such as those with acute ischemic stroke. Uric acid could also extend to more than 3 h the therapeutic window of rt-PA after stroke and it could limit the appearance of neurobehavioral changes after cardiopulmonary bypass. Prospective double blind randomized controlled trials are needed to test the value of uric acid in these clinical settings in which oxyradical formation is prominent. (C) 2003 Elsevier Ltd. All. rights reserved.