Intravenous uric acid administration significantly improved long-term outcomes in rodents following acute ischemic stroke, according to a groundbreaking preclinical study funded by the National Institutes of Health (NIH). The findings, published March 17, 2025, in the journal Stroke, suggest that uric acid could serve as a valuable adjunctive therapy to standard stroke treatments in humans.
The research, led by Dr. Enrique Leira and Dr. Anil Chauhan at the University of Iowa, Iowa City, utilized a well-established rodent model that closely mimics human stroke conditions. Researchers administered either intravenous uric acid or saline control to the animals and tracked their recovery over a one-month period using comprehensive behavioral and neurological assessments, including MRI scans.
Significant Improvements in Primary Outcomes
The study's primary outcome measure—sensorimotor function at 30 days post-stroke—showed marked improvement in mice treated with uric acid compared to the control group. Additionally, survival rates were significantly higher among animals receiving uric acid treatment. However, researchers noted that some secondary outcome measures, including the extent of brain damage, did not show reduction.
"These results are particularly encouraging because they demonstrate sustained benefits in function and survival, which are ultimately the most important outcomes for stroke patients," said Dr. Leira. "The fact that these improvements persisted for 30 days suggests uric acid may offer long-term neuroprotective effects."
Broad Efficacy Across Diverse Population Groups
A notable strength of the study was its inclusive design, which incorporated equal numbers of male and female animals, as well as subjects of varying ages and health conditions. The research team specifically included older mice, young mice, obese mice, and rats with hypertension—mirroring the diverse patient populations affected by stroke in clinical settings.
Uric acid demonstrated efficacy across all these groups, suggesting robust potential for human applications, particularly in patients with common stroke comorbidities. This broad effectiveness addresses a critical gap in stroke research, where treatments often show variable results across different patient populations.
Addressing a Critical Unmet Need
Ischemic stroke remains a leading cause of disability and death in the United States, occurring when blood supply to the brain is interrupted by a clot or blockage. While current standard treatments—including clot-busting medications and surgical interventions—are effective at restoring blood flow, many patients still experience incomplete recovery.
The researchers propose that uric acid could serve as a neuroprotective agent, administered either immediately before or during clot removal procedures, potentially enhancing the effectiveness of standard treatments and improving patient outcomes.
"What makes uric acid particularly promising is that it could be easily integrated into existing stroke treatment protocols," explained Dr. Chauhan. "As an add-on therapy, it wouldn't replace current approaches but rather complement them to provide additional protection for vulnerable brain tissue."
Rigorous Methodology Through SPAN Initiative
This study represents a significant output from the NIH's Stroke Preclinical Assessment Network (SPAN), an initiative designed to bring clinical trial rigor to preclinical research. SPAN employs standardized clinical practices such as randomization and blinded analysis in animal studies to identify agents with the highest likelihood of success in human trials.
In a comprehensive evaluation, SPAN recently tested six promising stroke treatments, with uric acid emerging as the only agent demonstrating significant efficacy. This rigorous vetting process substantially increases confidence in uric acid's potential clinical value.
"The SPAN approach addresses a persistent challenge in translational research—the gap between promising preclinical results and clinical efficacy," noted a spokesperson from the National Institute of Neurological Disorders and Stroke (NINDS), which partially funded the research. "By applying clinical trial standards to animal studies, we can better predict which treatments deserve investment in human trials."
Pathway to Clinical Translation
The researchers believe these findings provide compelling evidence for advancing uric acid into human clinical trials for stroke treatment. The next steps would likely involve safety studies and early-phase clinical trials to establish optimal dosing and timing of administration in human patients.
The study was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) (U01NS113388, U24NS113452) and the National Heart Lung and Blood Institute (R35HL139926).
The full research article, "Uric acid stroke cerebroprotection transcended sex, age, and comorbidities in a multicenter preclinical trial," was published in the March 17, 2025 issue of Stroke (DOI: 10.1161/STROKEAHA.124.048748).
