Effect of uric acid in animal models of ischemic stroke: A systematic review and meta-analysis

Aliena-Valero, A. and Baixauli-Martín, J. and Castelló-Ruiz, M. and Torregrosa, G. and Hervás, D. and Salom, J. B.

J Cereb Blood Flow Metab (2021) 41: 707–722

DOI: 10.1177/0271678x20967459

Abstract

Addition of uric acid (UA) to thrombolytic therapy, although safe, showed limited efficacy in improving patients’ stroke outcome, despite alleged neuroprotective effects of UA in preclinical research. This systematic review assessed the effects of UA on brain structural and functional outcomes in animal models of ischemic stroke. We searched Medline, Embase and Web of Science to identify 16 and 14 eligible rodent studies for qualitative and quantitative synthesis, respectively. Range of evidence met 10 of a possible 13 STAIR criteria. Median (Q1, Q3) quality score was 7.5 (6, 10) on the CAMARADES 15-item checklist. For each outcome, we used standardised mean difference (SMD) as effect size and random-effects modelling. Meta-analysis showed that UA significantly reduced infarct size (SMD: -1.18; 95% CI [-1.47, -0.88]; p \textless 0.001), blood-brain barrier (BBB) impairment/oedema (SMD: -0.72; 95% CI [-0.97, -0.48]; p \textless 0.001) and neurofunctional deficit (SMD: -0.98; 95% CI [-1.32, -0.63]; p \textless 0.001). Overall, there was low to moderate between-study heterogeneity and sizeable publication bias. In conclusion, published rodent data suggest that UA improves outcome following ischemic stroke by reducing infarct size, improving BBB integrity and ameliorating neurofunctional condition. Specific recommendations are given for further high-quality preclinical research required to better inform clinical research.

Citation

Aliena-Valero, A., Baixauli-Martín, J., Castelló-Ruiz, M., Torregrosa, G., Hervás, D., & Salom, J. B. (2021). Effect of uric acid in animal models of ischemic stroke: A systematic review and meta-analysis. J Cereb Blood Flow Metab, 41(4), 707–722. https://doi.org/10.1177/0271678x20967459 animal model, article., brain damage, Ischaemic stroke, ischemic stroke, neurofunctional deficit, of interest with respect to the research, authorship, and/or publication of this, uric acid

Keywords

• animal model
• article.
• brain damage
• Ischaemic stroke
• ischemic stroke
• neurofunctional deficit
• of interest with respect to the research
• authorship
• and/or publication of this
• uric acid