Abstract WP260: Uric Acid Reduces Infarct and Improves Neurological Function in Female Mice One Week After Transient Cerebral Ischemia

Abstract

Background & Purpose: Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and in human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. In accordance with STAIR-RIGOR criteria, confirmation of efficacy in alternative preclinical models is required before clinical trials can be initiated in the United States. To date, preclinical efficacy has only been established in the acute setting in male rodents. Methods: Seven to nine week old ovariectomized female mice were subjected to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry in all animals. A separate lab randomly assigned animals to vehicle vs uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Post-stroke analysis of infarction size and neurological function were conducted by investigators blind to treatment group, with a 7 day primary endpoint and intermediary analysis at 1and 3 days. Results: Infarct size and neurological function at 7 days post-stroke was significantly improved in uric acid-treated animals, relative to vehicle. Conclusions: Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a more chronic time point than has been investigated previously. These results supports STAIR-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke.