Evidence map›Paper›PMID 29687302›Full record

ArticleTranslational stroke research2019

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Maria E Ramos-Araque, Cristina Rodriguez, Rebeca Vecino, Elisa Cortijo Garcia, Mercedes de Lera Alfonso, Mercedes Sanchez Barba, Laura Colàs-Campàs, Francisco Purroy, Juan F Arenillas, Angeles Almeida and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Translational stroke research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Maria E Ramos-AraqueInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain.
Cristina RodriguezInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain.
Rebeca VecinoInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain.
Elisa Cortijo GarciaStroke Unit, Department of Neurology, University Hospital of Valladolid, University of Valladolid, Valladolid, Spain.
Mercedes de Lera AlfonsoStroke Unit, Department of Neurology, University Hospital of Valladolid, University of Valladolid, Valladolid, Spain.
Mercedes Sanchez BarbaInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain.
Laura Colàs-CampàsClinical Neurosciences Group, IRBLleida. UdL, Lleida, Spain.
Francisco PurroyClinical Neurosciences Group, IRBLleida. UdL, Lleida, Spain.
Juan F ArenillasStroke Unit, Department of Neurology, University Hospital of Valladolid, University of Valladolid, Valladolid, Spain.
Angeles AlmeidaInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain.
Maria Delgado-EstebanInstitute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Calle Zacarías González 2, 37007, Salamanca, Spain. mdesteban@usal.es.ORCID 0000-0002-6205-6611
Universidad de Salamanca · ESUniversidad de Valladolid · ESHospital Universitari Arnau de Vilanova · ESInstituto de Investigación Biomédica de Lleida · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Indexed as

AgedAged, 80 and overAnimalsApoptosisArginineBrain IschemiaCaspase 3Cell HypoxiaCells, CulturedCerebral CortexCohort StudiesElectron Transport Complex IVEmbryo, MammalianExcitatory Amino Acid AgonistsFemaleGlucoseArginineCaspase 3Electron Transport Complex IVExcitatory Amino Acid AgonistsGlucoseMicrotubule-Associated ProteinsMtap2 protein, mouseN-MethylaspartateProlineTrp53 protein, mouseTumor Suppressor Protein p53Ischemic toleranceNeuroprotectionPreconditioningTp53 Arg72Pro polymorphismTransient ischemic attack

Identifiers

PMID29687302
PMCPMC6421278
OpenAlexW2800476681

What OpenQuestion holds

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LicenceCC BY
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.