Uric acid administration in patients with acute stroke: a novel approach to neuroprotection.
Uric acid (UA) is the end product of purine catabolism in humans and is a powerful antioxidant whose generation is increased under ischemic conditions. However, both clinical and experimental studies reveal a gradual exhaustion of the antioxidant capacity after transient cerebral ischemia, and the magnitude of this consumption seems to be correlated with the extent of brain tissue injury, growth of the infarction, severity of neurological impairment in the acute phase, and long-term functional outcome. Growing evidence supports the neuroprotective effect of UA administration after brain ischemia. In experimental conditions, the administration of UA is neuroprotective both in mechanical models of brain ischemia (transient or permanent intraluminal occlusion of the middle cerebral artery) and in thromboembolic models of autologous clot injection. The administration of UA is feasible and safe in healthy volunteers. In acute stroke patients treated with recombinant tissue plasminogen activator (rt-PA), co-administration of UA has proven to reduce lipid peroxidation and to prevent the fall in UA blood levels that occur very early after stroke onset. Currently, a multicentric Phase III clinical trial is testing whether the administration of UA increases the clinical benefits of rt-PA, which represents the only approved therapy in patients with acute ischemic stroke. This review summarizes the available information justifying such a novel therapeutic approach in this devastating clinical condition.
Amaro
Sergio
S
Stroke Unit, Department of Neurological Sciences, Hospital Clínic Barcelona. 170 Villarroel, 08036, Barcelona, Spain. sergiamde@hotmail.com
Planas
Anna M
AM
Chamorro
Angel
A
D000818:Animals; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D014527:Uric Acid / Q000008:administration & dosage*
D018696:Neuroprotective Agents; D014527:Uric Acid