Evidence map›Paper›PMID 33401017›Full record

ArticleBrain, behavior, and immunity2021

Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood-brain barrier damage, and inflammation.

Jonas Leinweber, Daniella M Mizurini, Ivo M B Francischetti, Michael Fleischer, Dirk M Hermann, Christoph Kleinschnitz, Friederike Langhauser

Open access · greenAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% 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, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. ShSPI Inhibits Thrombosis Formation and Ischemic Stroke In Vivo.International journal of molecular sciences · 2024
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Brain Ischemia as a Prelude to Alzheimer's Disease.Frontiers in aging neuroscience · 2021
    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

7 authors at 4 institutions in 3 countries.

Jonas LeinweberDepartment of Neurology of University Hospital Würzburg, Josef-Schneider-Straße 2, 97080 Würzburg, Germany.
Daniella M MizuriniInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Ivo M B FrancischettiLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael FleischerDepartment of Neurology of University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany.
Dirk M HermannDepartment of Neurology of University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany.
Christoph KleinschnitzDepartment of Neurology of University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany.
Friederike LanghauserDepartment of Neurology of University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany. Electronic address: Friederike.Langhauser@uk-essen.de.
Essen University Hospital · DENational Institutes of Health · USUniversidade Federal do Rio de Janeiro · BRUniversitätsklinikum Würzburg · DE

Funding

Vector-Borne Diseases: Biology Of Vector Host RelationshipZ01AI000810 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI RIBEIRO, JOSE M · 1997 to 2008
$3.5M
Intramural NIH HHS Z01 AI000810
6 · The paper itself

Abstract

Recently it was shown that the hematophagous salivary gland protein agaphelin exhibits multiple antithrombotic effects without promoting the risk of bleeding. Agaphelin inhibits neutrophil elastase and thereby reduces cathepsin G-induced platelet aggregation. However, it is still unclear, whether pharmacological treatment with agaphelin in brain ischemia is protective and, regarding its bleeding risk, safe. To elucidate this issue, male C57BL/6 mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) and treated with 0.25 mg/kg agaphelin intravenously immediately after tMCAO. On day 1 and 7, infarct volume and functional neurological outcome were assessed by behavioural tests, histochemistry and magnetic resonance imaging. Thrombus formation, intracerebral bleeding risk, blood-brain barrier damage and the local inflammatory response were determined on day 1. This study shows for the first time a protective effect of agaphelin characterized by smaller infarct volume, reduced neurological deficits and reduced animal mortality. This protective effect was associated with reduced local thrombus formation, increased blood-brain barrier integrity and reduced brain inflammatory response. It is essential to mention that the protective effect of agaphelin was not linked to an increased risk of intracerebral bleeding. The promotion of brain tissue survival and inhibition of thromboinflammation identifies agaphelin as a promising treatment option in ischemic stroke, which considering the lack of bleeding risk should potentially be safe.

Indexed as

Brain IschemiaIschemic StrokeThrombosisAnimalsBlood-Brain BarrierDisease Models, AnimalInfarction, Middle Cerebral ArteryInflammationInsect ProteinsMaleMiceMice, Inbred C57BLPancreatic ElastaseSalivary Proteins and Peptidesagaphelin protein, Anopheles gambiaeInsect ProteinsPancreatic ElastaseSalivary Proteins and PeptidesAgaphelinAntithromboticApoptosisBleeding complicationBlood-brainbarrierExperimental strokeInflammationNeutrophil elastase inhibitorThromboinflammationThrombosis

Identifiers

PMID33401017
PMCPMC7979502
OpenAlexW3118333096

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.