Evidence map›Paper›PMID 27032444›Full record

SynthesisStroke2016

Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective Pooled Analysis.

Cyrille Orset, Benoit Haelewyn, Stuart M Allan, Saema Ansar, Francesco Campos, Tae Hee Cho, Anne Durand, Mohamad El Amki, Marc Fatar, Isaac Garcia-Yébenes and 18 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in Stroke, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Photothrombolytics: A light-driven technology for the targeted lysis of thrombi.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  5. Review
  6. Article
  7. Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Neural cortical organoids from self-assembling human iPSC as a model to investigate neurotoxicity in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
  13. Review
  14. Article
  15. Article
  16. Optimized mouse model of embolic MCAO: From cerebral blood flow to neurological outcomes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  17. Article
  18. Review
  19. Review
  20. Review
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

28 authors at 1 institution in 2 countries.

Cyrille OrsetInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Benoit HaelewynExperimental Stroke Research Platform, CURB, University Caen Normandie, Caen, France.
Stuart M AllanUniversity of Manchester, Faculty of Medical and Health Sciences, Manchester, United Kingdom.
Saema AnsarNeurologische Universitätsklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Francesco CamposDept of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Tae Hee ChoInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Anne DurandDept of Stroke Medicine and Department of Neuroradiology; Université Lyon 1; CREATIS, CNRS UMR 5220-INSERM U1044 ; Hospices Civils de Lyon ; Lyon, France.
Mohamad El AmkiEA4475 Pharmacologie de la Circulation Cérébrale, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Marc FatarDepartment of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Germany.
Isaac Garcia-YébenesUnidad de Investigación Neurovascular, Departamento Farmacología, Facultad de Medicina, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Maxime GaubertiInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Saskia GrudzenskiDepartment of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Germany.
Ignacio LizasoainUnidad de Investigación Neurovascular, Departamento Farmacología, Facultad de Medicina, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Eng LoDepartments of Radiology, and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.
Richard MacrezInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Isabelle MargaillEA4475 Pharmacologie de la Circulation Cérébrale, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Samaneh MaysamiUniversity of Manchester, Faculty of Medical and Health Sciences, Manchester, United Kingdom.
Stephen MeairsNeurologische Universitätsklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Norbert NighoghossianDept of Stroke Medicine and Department of Neuroradiology; Université Lyon 1; CREATIS, CNRS UMR 5220-INSERM U1044 ; Hospices Civils de Lyon ; Lyon, France.
Josune OrbeInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Jose Antonio ParamoLaboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA-University of Navarra, Pamplona, Spain.
Jean-Jacques ParientiDepartments of Biostatistics and Clinical Research, Centre Hospitalier Universitaire (CHU), Caen ; EA4655 Risques Microbiens, Université de Caen Normandie, Caen, France.
Nancy J RothwellUniversity of Manchester, Faculty of Medical and Health Sciences, Manchester, United Kingdom.
Marina RubioInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Christian WaeberDept of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Alan R YoungInserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Emmanuel Touzé *Inserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Denis Vivien *Inserm UMR-S U919, University Caen Normandie, GIP Cyceron, Caen, France.
Inserm · FR

Funding

Targeting ROCK for Neurogliovascular Plasticity & Remodeling After StrokeP01NS055104 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2007 to 2018
$13.3M
Neuron-Dervied S1P and Endothelial Function in StrokeR01NS049263 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WAEBER, CHRISTIAN · 2006 to 2010
$1.9M
NINDS NIH HHS P01 NS055104NINDS NIH HHS R01 NS049263
6 · The paper itself

Abstract

background and purposeThe debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator.

methodsWe collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (<3 hours) versus late (≥3 hours) drug administration. Final infarct volumes, assessed by histology or magnetic resonance imaging, were compared in each study, and the absolute differences were pooled in a random-effect meta-analysis. The influence of time of administration was tested.

resultsWhen compared with saline controls, early recombinant tissue-type plasminogen activator administration was associated with a significant benefit (absolute difference, -6.63 mm(3); 95% confidence interval, -9.08 to -4.17; I(2)=76%), whereas late recombinant tissue-type plasminogen activator treatment showed a deleterious effect (+5.06 mm(3); 95% confidence interval, +2.78 to +7.34; I(2)=42%; Pint<0.00001). Results remained unchanged after subgroup analyses.

conclusionsOur results provide the basis needed for the design of future preclinical studies on recanalization therapies using this model of thromboembolic stroke in mice. The power analysis reveals that a multicenter trial would require 123 animals per group instead of 40 for a single-center trial.

Indexed as

AnimalsBrain IschemiaDisease Models, AnimalFibrinolytic AgentsInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLStrokeTissue Plasminogen ActivatorFibrinolytic AgentsTissue Plasminogen Activatormagnetic resonance imagingmiddle cerebral arterystrokethrombolytic therapytissue-type plasminogen activator

Identifiers

PMID27032444
PMCPMC4846545
OpenAlexW2329112309

What OpenQuestion holds

Textmetadata
LicenceTDM
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.