Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke

Llull, Laura; Laredo, Carlos; Renú, Arturo; Pérez, Belén; Vila, Elisabet; Obach, Vı́ctor; Urra, Xabier; Planas, Anna M.; Amaro, Sergio; Chamorro, Ángel

doi:10.1161/strokeaha.115.009960

Cited by 107 publications

(81 citation statements)

References 36 publications

(43 reference statements)

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“…A follow-up, multicenter, biomarker-driven, placebo-controlled phase II study (SURE-ALS2) is in the planning stages and is scheduled to begin enrollment in early 2017. Encouraging clinical results were also recently obtained by the Safety and Efficacy of Uric Acid in Patients with Acute Stroke (URICO-ICTUS) study: a phase IIb/III randomized, double-blind trial of intravenous urate administration within a few hours of stroke onset [42,43]. In this study, the combination of urate treatment with thrombolysis in acute ischemic stroke resulted in improved clinical outcomes in women but not men.…”

Section: Pre-pdmentioning

confidence: 78%

“…Neuroprotective [35] Neuroprotective in SCI, brain ischemia/stroke, MS [38][39][40][41] Clinical trials SURE-PD (phase II trial) [10] URICO-ICTUS (phase IIb/III trial in stroke) [42,43] PD = Parkinson's disease; ALS = amyotrophic lateral sclerosis; AD = Alzheimer's disease; HD = Huntington's disease; MSA = multiple system atrophy; MCI = mild cognitive impairment; SCI = spinal cord injury; MS = multiple sclerosis …”

Section: In Vivomentioning

confidence: 99%

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Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Paganoni

Schwarzschild

2017

Neurotherapeutics

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Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration.

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Section: Pre-pdmentioning

confidence: 78%

Section: In Vivomentioning

confidence: 99%

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Paganoni

Schwarzschild

2017

Neurotherapeutics

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“…Secondary reanalysis were proceeded in different subpopulations, and it turned out, that in the woman subpopulation and among patients with hyperglycemia during acute stroke the uric acid administration with rtPA raised the number of excellent outcome and increased infarct growth in comparison to placebo. Hyperglycemia greatly increases ROS burden, and uric acid -as an antioxidant -is supposed to perform its positive effect in the way of ROS neutralizing [163,164].…”

Section: Uric Acidmentioning

confidence: 99%

Hemorrhagic transformation of ischemic stroke

J¹,

Hortobágyi²

2017

Vascul Dis Ther

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The better understanding of the diverse mechanisms leading to the hemorrhagic transformation of an ischemic stroke is the crucial point in the prevention of this altogether common phenomenon. The different individual risk factors include the anatomical variability of collateral blood supply, age, genetics, body weight, etiology of the occlusion, side of the occluded vessel, renal status, stroke severity, history of high serum glucose or hypertension and hypertension or hyperglycemia at the onset of the stroke, ferritin level, INR, antiplatelet usage or the platelet count etc. All these might contribute to the process of hemorrhagic transformation. These risk factors have been identified by retrospective epidemiological studies and are useful to identify patients who are at high risk for hemorrhagic conversion and help the decision between conservative, thrombolytic or more advanced treatments such as thrombectomy. The modulations of potential molecular targets participating in the process seem to be promising in animal models, but human trials are lacking the breakthrough success so far, both in extending the time frame of the thrombolysis and in replacing the recombinant tissue plasminogen activator (rtPA) as thrombolytic agent.So far, the careful preselection of patients eligible for thrombolytic therapy is the best way to prevent hemorrhagic transformation. The intensive research in the field revealing small but important molecular details are continuously contributing to the better understanding of hemorrhagic transformation with the intention of finding new agents that co-administrated to the rtPA or completely replacing that could decrease the risk of secondary bleeding.The aim of this review is to give comprehensive insight into the process of hemorrhagic transformation of ischemic stroke, starting with basic overview of the penumbra concept and the collateral supply followed by discussion of the recanalisation-reperfusion-hemorrhagic transformation process after vessel occlusion also highlighting the importance of timing and ratio of recanalisation spontaneously and in case of thrombolytic agent administration. We overview the risk factors of hemorrhagic transformation, which may be helpful to physicians to identify high risk patients before rtPA administration. The last part of the work is dealing with future therapeutic possibilities based on the so far revealed molecular mechanisms of hemorrhagic transformation. With the aim to assess the rate and influencing factors on the recanalisation and reperfusion rate 381 patients with large-vessel occlusion was investigated. The patient group involved ones treated with rtPA or treated conservatively. Partial or complete recanalisation was achieved in 121 out of 210 (58%) patients after intravenous rtPA administration. The recanalisation success was more likely if the patient had atrial fibrillation [4] -maybe because cardioembolic clots consists more fibrin and are more likely to reopen by plasmin proteolysis than thrombosis of an atherosclerotic plaq...

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“…There have been several advances in the field of neuroprotective strategies (Table 1) [16,17,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36].…”

Section: Recent Advances and Future Per-spectivementioning

confidence: 99%

“…Remote ischemic postconditioning within 24 hours after stroke onset was safe and feasible, and may improve outcome (RECAST) [32]. Remote ischemic preconditioning was safe in patients undergoing carotid artery stenting, which may decrease iatrogenic ischemic brain injury [48].…”

Section: Magnesiummentioning

confidence: 99%

Neuroprotective strategies for acute ischemic stroke: recent progress and future perspectives

Bang

2017

Precis Future Med

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Stroke is one of the leading causes of death and most common cause of disability in adult. Despite of recent advances in the recanalization therapy for acute ischemic stroke, the need for neuroprotectants is substantial, to extend the window for recanalization therapy and to prevent neuronal death by ischemic brain injury or by reperfusion injury after successful therapy. Herein, the possible reasons for the failure of neuroprotectants trials during the past two decades and current status of neuroprotective strategies for acute ischemic stroke are discussed. This review will also address the recent advances and future perspectives in preclinical and clinical trials of neuroprotective agents, including the efforts of high quality of transition of preclinical results to clinical trial, genetic studies to trigger neuroprotectants development, application of neuroprotectants at optimal time and duration after stroke, adjuvant approaches, and biomarker-based triage.

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Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke

Cited by 107 publications

References 36 publications

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Hemorrhagic transformation of ischemic stroke

Neuroprotective strategies for acute ischemic stroke: recent progress and future perspectives

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