Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia

Nirav Dhanesha; Edwin Vázquez-Rosa; Coral J Cintrón-Pérez; Daniel Thedens; Alexa J Kort; Vicky Chuong; Adriana M Rivera-Dompenciel; Anil K Chauhan; Enrique C Leira; Andrew A Pieper

doi:10.1016/j.jstrokecerebrovasdis.2017.12.043

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Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia

Journal article

Peer reviewed

Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia

Nirav Dhanesha, Edwin Vázquez-Rosa, Coral J Cintrón-Pérez, Daniel Thedens, Alexa J Kort, Vicky Chuong, Adriana M Rivera-Dompenciel, Anil K Chauhan, Enrique C Leira and Andrew A Pieper

Journal of stroke and cerebrovascular diseases, Vol.27(5), pp.1412-1416

02/01/2018

DOI: 10.1016/j.jstrokecerebrovasdis.2017.12.043

PMID: 29398531

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Abstract

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. 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. Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. 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.

Stroke

animal model

uric acid

neuroprotection

Details

Title: Subtitle: Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia
Creators: Nirav Dhanesha - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Edwin Vázquez-Rosa - 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
Coral J Cintrón-Pérez - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Daniel Thedens - Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Alexa J Kort - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Vicky Chuong - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Adriana M Rivera-Dompenciel - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Anil K Chauhan - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: anil-chauhan@uiowa.edu
Enrique C Leira - 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
Andrew A Pieper - 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
Resource Type: Journal article
Publication Details: Journal of stroke and cerebrovascular diseases, Vol.27(5), pp.1412-1416
DOI: 10.1016/j.jstrokecerebrovasdis.2017.12.043
PMID: 29398531
NLM abbreviation: J Stroke Cerebrovasc Dis
ISSN: 1052-3057
eISSN: 1532-8511
Publisher: Elsevier Inc; United States
Grant note: name: University of Iowa Carver College of Medicine Pilot Grant; name: Mary Alice Smith Fund for Neuropsychiatry Research; name: Titan Neurological Research Fund; name: Brockman Medical Research Foundation
Language: English
Date published: 02/01/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Psychiatry; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Psychological and Brain Sciences; Iowa Neuroscience Institute; Radiation Oncology; Neurosurgery; Internal Medicine
Record Identifier: 9984020754402771

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