Serum uri acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study

Abstract

BackgroundA possible synergic role of serum uric acid (SUA) with thrombolytic therapies is controversial and needs further investigations. We therefore evaluated association of admission SUA with clinical improvement and clinical outcome in patients receiving rt-PA, early admitted patients not receiving rt-PA, and patients admitted after time window for rt-PA.MethodsSUA levels were obtained at admission and categorized as low, middle and high, based on 33° and 66° percentile values. Patients were categorized as patients admitted within 3 hours of symptom onset receiving rt-PA (rt-PA group), patients admitted within 3 hours of symptom onset not receiving rt-PA (non-rt-PA group), and patients admitted after time window for rt-PA (late group). Short-term clinical improvement was defined as the difference between NIHSS on admission minus NIHSS day 7. Favorable outcome was defined as mRS 0 - 3 and unfavorable outcome as mRS 4 - 6.ResultsSUA measurements were available in 1136 patients. Clinical improvement was significantly higher in patients with high SUA levels at admission. After adjustment for possible confounders, SUA level showed a positive correlation with clinical improvement (r = 0.012, 95% CI 0.002-0.022, p = 0.02) and was an independent predictor for favorable stroke outcome (OR 1.004; 95% CI 1.0002-1.009; p = 0.04) only in the rt-PA group.ConclusionsSUA may not be neuroprotective alone, but may provide a beneficial effect in patients receiving thrombolysis.

The effect of erythropoietin on serum uric acid levels during renal ischemia reperfusion injury in rats

“…Patients with low SUA concentrations of ≤4.5 mg/dL had more favorable outcomes after a month of follow-up (p=0.004), marking the magnitude of the cerebral infarction. However, significantly higher clinical improvement in AIS patients was found, [4] with high SUA levels at admission. SUA levels showed a positive correlation with clinical improvement (p=0.02) and acted as an independent predictor for favorable stroke outcome (p=0.04) in the thrombolysis group.…”

Evaluation of serum uric acid in acute ischaemic stroke

“…There are only few studies that have concluded higher levels of serum uric acid being neuroprotective in patients with stroke. 5,[7][8][9] An explanation to this comes from the study which concluded that serum uric acid can work as pro-oxidant under certain circumstances, particularly if the levels of other antioxidants like ascorbic acid are low. 31 Various studies have shown that uric acid can result in endothelial dysfunction which can lead to vascular disease.…”

“…5,[7][8][9] Therefore the role of uric acid as a risk factor for acute ischemic stroke is controversial. Hence the present study was conducted to determine risk factor potential of serum uric acid levels in patients with acute ischemic stroke.…”

New possibilities of neuroprotection in ischemic stroke

“…Среди фармакологических препаратов, которые в настоящее время изучаются в качест-ве дополнения к алтеплазе, следует отметить мочевую кис-лоту, однократное внутривенное применение которой в до-зе 1 г в комбинации с системным тромболизисом изучается в многоцентровом исследовании 2/3-й фазы [63]. Ранее бы-ло показано, что уровень эндогенной мочевой кислоты на момент проведения тромболизиса коррелирует с благопри-ятным исходом лечения [64].…”

“…Среди фармакологических препаратов, которые в настоящее время изучаются в качест-ве дополнения к алтеплазе, следует отметить мочевую кис-лоту, однократное внутривенное применение которой в до-зе 1 г в комбинации с системным тромболизисом изучается в многоцентровом исследовании 2/3-й фазы [63]. Ранее бы-ло показано, что уровень эндогенной мочевой кислоты на момент проведения тромболизиса коррелирует с благопри-ятным исходом лечения [64].З а к л ю ч е н и е Детальное знание патофизиологии ишемического по-вреждения ткани головного мозга и наличие огромного ко-личества веществ, потенциально способных повлиять на исход ишемии, пока так и не позволили создать нейропро-текторные препараты, обладающие однозначно доказанной клинической эффективностью. Причинами этого являются как далекие от идеала подходы к доклиническим исследова-ниям веществ-кандидатов, обусловленные выраженной ге-терогенностью инсульта у человека по сравнению с лабора-торной моделью, так и, возможно, недостаточная обосно-ванность изолированного применения нейропротекторов без реперфузии.…”