Evidence map›Paper›PMID 37848338›Full record

ReviewNeurology2023

Uric Acid: A Translational Journey in Cerebroprotection That Spanned Preclinical and Human Data.

Enrique C Leira, Anna M Planas, Anil K Chauhan, Angel Chamorro

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 2 countries.

Enrique C LeiraFrom the Department of Neurology (E.L., A.C.), and Departments of Neurosurgery & Epidemiology (E.L.), University of Iowa, Iowa City; Institute of Biomedical Research of Barcelona (IIBB) (A.M.P.), Spanish National Research Council (CSIC); August Pi i Sunyer Biomedical Research Institute (IDIBAPS) (A.M.P., A.C.), Barcelona, Spain; Department of Internal Medicine (A.K.C.), University of Iowa, Iowa City; and Hospital Clinic (A.C.), University of Barcelona, Spain.ORCID 0000-0003-3695-2946
Anna M PlanasFrom the Department of Neurology (E.L., A.C.), and Departments of Neurosurgery & Epidemiology (E.L.), University of Iowa, Iowa City; Institute of Biomedical Research of Barcelona (IIBB) (A.M.P.), Spanish National Research Council (CSIC); August Pi i Sunyer Biomedical Research Institute (IDIBAPS) (A.M.P., A.C.), Barcelona, Spain; Department of Internal Medicine (A.K.C.), University of Iowa, Iowa City; and Hospital Clinic (A.C.), University of Barcelona, Spain.ORCID 0000-0002-6147-1880
Anil K ChauhanFrom the Department of Neurology (E.L., A.C.), and Departments of Neurosurgery & Epidemiology (E.L.), University of Iowa, Iowa City; Institute of Biomedical Research of Barcelona (IIBB) (A.M.P.), Spanish National Research Council (CSIC); August Pi i Sunyer Biomedical Research Institute (IDIBAPS) (A.M.P., A.C.), Barcelona, Spain; Department of Internal Medicine (A.K.C.), University of Iowa, Iowa City; and Hospital Clinic (A.C.), University of Barcelona, Spain.ORCID 0000-0001-8554-0898
Angel ChamorroFrom the Department of Neurology (E.L., A.C.), and Departments of Neurosurgery & Epidemiology (E.L.), University of Iowa, Iowa City; Institute of Biomedical Research of Barcelona (IIBB) (A.M.P.), Spanish National Research Council (CSIC); August Pi i Sunyer Biomedical Research Institute (IDIBAPS) (A.M.P., A.C.), Barcelona, Spain; Department of Internal Medicine (A.K.C.), University of Iowa, Iowa City; and Hospital Clinic (A.C.), University of Barcelona, Spain. achamorro@clinic.cat.ORCID 0000-0002-0392-6285
University of Iowa · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Uric acid (UA) is a strong endogenous antioxidant that neutralizes the toxicity of peroxynitrite and other reactive species on the neurovascular unit generated during and after acute brain ischemia. The realization that a rapid reduction of UA levels during an acute ischemic stroke was associated with a worse stroke outcome paved the way to investigate the value of exogenous UA supplementation to counteract the progression of redox-mediated ischemic brain damage. The long translational journey for UA supplementation recently reached a critical milestone when the results of the multicenter NIH stroke preclinical assessment network (SPAN) were reported. In a novel preclinical paradigm, 6 treatment candidates including UA supplementation were selected and tested in 6 independent laboratories following predefined criteria and strict methodological rigor. UA supplementation was the only intervention in SPAN that exceeded the prespecified efficacy boundary with male and female animals, young mice, young rats, aging mice, obese mice, and spontaneously hypertensive rats. This unprecedented achievement will allow UA to undergo clinical testing in a pivotal clinical trial through a NIH StrokeNet thrombectomy endovascular platform created to assess new treatment strategies in patients treated with mechanical thrombectomy. UA is a particularly appealing adjuvant intervention for mechanical thrombectomy because it targets the microcirculatory hypoperfusion and oxidative stress that limits the efficacy of this therapy. This descriptive review aims to summarize the translational development of UA supplementation, highlighting those aspects that likely contributed to its success. It includes having a well-defined target and mechanism of action, and an approach that simultaneously integrated rigorous preclinical assessment, with epidemiologic and preliminary human intervention studies. Validation of the clinical value of UA supplementation in a pivotal trial would confirm the translational value of the SPAN paradigm in preclinical research.

Indexed as

Brain IschemiaIschemic StrokeStrokeAnimalsFemaleHumansMaleMiceMicrocirculationMulticenter Studies as TopicRatsUric AcidUric Acid

Identifiers

PMID37848338
PMCPMC10752646
OpenAlexW4387698847

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.