Uric Acid in Cerebral Ischemia: A Systematic Review of Its Biomarker Value and Role in Neuroprotection

Uric acid (UA), the end product of purine metabolism, exhibits dual roles in cerebral ischemia-it functions as a cerebroprotective antioxidant in acute settings and as a pro-oxidant contributor to vascular damage in chronic conditions. Some studies suggest that higher UA levels may confer protection during the acute phase of stroke, particularly in subgroups such as women, hyperglycemic patients, and thrombectomy recipients. In contrast, chronic hyperuricemia has been consistently linked to adverse cardiovascular outcomes, increased stroke recurrence, and poor recovery. A systematic review was conducted in accordance with PRISMA 2020 guidelines. MEDLINE, Google Scholar, and the Cochrane Library were searched up to April 2025. Eligible studies included adults with acute ischemic stroke in whom UA levels were reported within 72 h of onset. Primary outcomes were mortality, functional outcome (mRS), and neurological deterioration. Thirty-five studies involving over 15,000 patients were included. Evidence regarding UA's prognostic value was heterogeneous. Approximately 80% of studies identified high UA levels as being associated with increased mortality, stroke recurrence, or disability. However, randomized trials-notably the URICO-ICTUS trial-suggested short-term neuroprotective effects in specific subgroups. Several studies also reported U- or J-shaped relationships, indicating that both low and high UA levels may adversely affect outcomes. Uric acid demonstrates a paradoxical role in cerebral ischemia. Acute-phase antioxidant effects may offer therapeutic potential, whereas chronic hyperuricemia is more often associated with vascular injury and worse long-term outcomes. UA may serve as a useful biomarker when incorporated into multifactorial prognostic models, but further well-controlled studies are needed to clarify its clinical utility in stroke prognosis and treatment.