Nirav Dhanesha1, Edwin Vázquez-Rosa2, Coral J Cintrón-Pérez3, Daniel Thedens4, Alexa J Kort3, Vicky Chuong3, Adriana M Rivera-Dompenciel3, Anil K Chauhan5, Enrique C Leira6, Andrew A Pieper7. 1. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 2. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 3. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 4. Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 5. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: anil-chauhan@uiowa.edu. 6. Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa. Electronic address: enrique-leira@uiowa.edu. 7. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: AndrewAPieper@gmail.com.
Abstract
BACKGROUND: 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 human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. METHODS: To address this need, we subjected 7- to 9-week old ovariectomized female mice 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. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. RESULTS: Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. CONCLUSION: Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-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. Published by Elsevier Inc.
BACKGROUND: 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 humanstrokepatients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. METHODS: To address this need, we subjected 7- to 9-week old ovariectomized female mice 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. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. RESULTS:Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. CONCLUSION: Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-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. Published by Elsevier Inc.
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