Evidence map›Paper›PMID 34546355›Full record

ArticleBlood advances2021

The brain-derived neurotrophic factor prompts platelet aggregation and secretion.

Imane Boukhatem, Samuel Fleury, Melanie Welman, Jessica Le Blanc, Chantal Thys, Kathleen Freson, Myron G Best, Thomas Würdinger, Bruce G Allen, Marie Lordkipanidzé

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.8field-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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
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  15. The intriguing role of platelets as custodians of brain-derived neurotrophic factor.Research and practice in thrombosis and haemostasis · 2024
    Article
  16. Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress.Research and practice in thrombosis and haemostasis · 2023
    Article
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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

10 authors at 3 institutions in 3 countries.

Imane BoukhatemFaculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.ORCID 0000-0002-3494-876X
Samuel FleuryFaculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.ORCID 0000-0002-6764-3700
Melanie WelmanResearch Center, Montreal Heart Institute, Montréal, QC, Canada.ORCID 0000-0002-9405-6712
Jessica Le BlancFaculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.ORCID 0000-0001-8454-9807
Chantal ThysDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Kathleen FresonDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.ORCID 0000-0002-4381-2442
Myron G BestDepartment of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands; and.
Thomas WürdingerDepartment of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands; and.
Bruce G AllenResearch Center, Montreal Heart Institute, Montréal, QC, Canada.ORCID 0000-0001-9000-9495
Marie LordkipanidzéFaculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.ORCID 0000-0001-7418-6766
Montreal Heart Institute · CAAmsterdam University Medical Centers · NLKU Leuven · BE

Funding

CIHR PJT-159569
6 · The paper itself

Abstract

Brain-derived neurotrophic factor (BDNF) has both autocrine and paracrine roles in neurons, and its release and signaling mechanisms have been extensively studied in the central nervous system. Large quantities of BDNF have been reported in circulation, essentially stored in platelets with concentrations reaching 100- to 1000-fold those of neurons. Despite this abundance, the function of BDNF in platelet biology has not been explored. At low concentrations, BDNF primed platelets, acting synergistically with classical agonists. At high concentrations, BDNF induced complete biphasic platelet aggregation that in part relied on amplification from secondary mediators. Neurotrophin-4, but not nerve growth factor, and an activating antibody against the canonical BDNF receptor tropomyosin-related kinase B (TrkB) induced similar platelet responses to BDNF, suggesting TrkB could be the mediator. Platelets expressed, both at their surface and in their intracellular compartment, a truncated form of TrkB lacking its tyrosine kinase domain. BDNF-induced platelet aggregation was prevented by inhibitors of Ras-related C3 botulinum toxin substrate 1 (Rac1), protein kinase C, and phosphoinositide 3-kinase. BDNF-stimulated platelets secreted a panel of angiogenic and inflammatory cytokines, which may play a role in maintaining vascular homeostasis. Two families with autism spectrum disorder were found to carry rare missense variants in the BDNF gene. Platelet studies revealed defects in platelet aggregation to low concentrations of collagen, as well as reduced adenosine triphosphate secretion in response to adenosine diphosphate. In summary, circulating BDNF levels appear to regulate platelet activation, aggregation, and secretion through activation of a truncated TrkB receptor and downstream kinase-dependent signaling.

Indexed as

Autism Spectrum DisorderBrain-Derived Neurotrophic FactorHumansPhosphatidylinositol 3-KinasesPlatelet ActivationPlatelet AggregationBrain-Derived Neurotrophic FactorPhosphatidylinositol 3-Kinases

Identifiers

PMID34546355
PMCPMC8945584
OpenAlexW3201447830

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.