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

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 ischaemic 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 < 0.001), blood-brain barrier (BBB) impairment/oedema (SMD: −0.72; 95% CI [−0.97, −0.48]; p < 0.001) and neurofunctional deficit (SMD: −0.98; 95% CI [−1.32, −0.63]; p < 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 ischaemic 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.

A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke

“…In addition, the somewhat smaller infarct size in SPAN compared with other stroke studies may have limited our ability to detect a reduction in infarct size. In prior studies, uric acid did show an effect on lesion volumes using different modalities of infarct volume assessments and times of observations; this finding will require confirmation (55,56).…”

“…Exogenous supplementation with uric acid has been studied in stroke patients and appears to be promising. The preclinical development of IV uric acid supplementation included demonstration of efficacy in reperfusion models that included different species, sex, and comorbidities, as well as synergy with IV recombinant tissue plasminogen activator (rtPA) ( 55 – 57 ). Our data support further clinical evaluation of uric acid supplementation as a potential treatment for acute ischemic stroke.…”

Efficacy and Safety of Panax notoginseng Saponins in the Treatment of Adults With Ischemic Stroke in China

“…Although α 4 integrin inhibition has been demonstrated in preclinical studies to provide neuroprotective benefits in models of focal cerebral ischemia, the results from a clinical trial did not support the efficacy of natalizumab in treating patients with ischemic stroke . Furthermore, translation from preclinical to clinical studies has been difficult in other neuroprotective agents, such as albumin, uric acid, and magnesium sulfate . The potential neuroprotective agents mentioned above shared a common feature: single-agent therapy.…”

Serum uric acid and dementia subtype

“…Namely, there is a possibility that reduced serum UA might be caused by the need to repair brain damage and reduce the development of VaD. This speculation should be checked by further experimental studies [7].…”