Evidence map›Paper›PMID 42446942›Full record

ArticleThe Journal of clinical investigation2026

Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.

Alessandro de Sa Pinheiro, Douglas E Teixeira, Rodrigo P Silva-Aguiar, Young Jun Shim, Alona A Merkulova, Sadiq Silbak, Yelenna Skomorovska-Prokvolit, David Midem, Sidney Ogolla, Bjoern B Burckhardt and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Alessandro de Sa PinheiroCase Western Reserve University, Cleveland, Ohio, USA.
Douglas E TeixeiraFederal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Rodrigo P Silva-AguiarCase Western Reserve University, Cleveland, Ohio, USA.
Young Jun ShimCleveland Clinic, Cleveland, Ohio, USA.
Alona A MerkulovaCase Western Reserve University, Cleveland, Ohio, USA.
Sadiq SilbakCase Western Reserve University, Cleveland, Ohio, USA.
Yelenna Skomorovska-ProkvolitCase Western Reserve University, Cleveland, Ohio, USA.
David MidemChulaimbo Sub-County Hospital, Kisumu, Kenya.
Sidney OgollaKenya Medical Research Institute, Kisumu, Kenya.
Bjoern B BurckhardtPharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Muenster, Germany.
Tanja GangnusPharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Muenster, Germany.
Julio ScharfsteinFederal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Celso Caruso-NevesFederal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Owen Jt McCartyOregon Health & Science University, Portland Oregon, USA.
David GailaniVanderbilt University Medical Center, Nashville, Tennessee, USA.
Michael BaderMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Charité - University Medicine, Berlin, Germany.
Philip J RosenthalUniversity of California, San Francisco, San Francisco, California, USA.
Arlene E DentCase Western Reserve University, Cleveland, Ohio, USA.
Chris J JanseLeiden University Medical Center, Leiden, Netherlands.
Keith R McCraeCleveland Clinic, Cleveland, Ohio, USA.
Ana Acacia de Sa PinheiroFederal University of Rio de Janeiro, Rio de Janeiro, Brazil.
James W KazuraCase Western Reserve University, Cleveland, Ohio, USA.
Alvin H SchmaierCase Western Reserve University, Cleveland, Ohio, USA.

Funding

Novel approaches to improve prediction of cancer-associated thrombosisU01HL143402 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI KHORANA, ALOK A, MCCRAE, KEITH R. · 2018 to 2022
$4.7M
Kruppel-Like Factor 2 Counters Vascular and Immunologic Dysfunction in Child Cerebral MalariaR01AI130131 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI KAZURA, JAMES WALTER · 2017 to 2021
$3.0M
Tyrosine Kinases and ThrombosisR01HL157405 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI SCHMAIER, ALVIN H · 2022 to 2025
$1.9M
Chromatin Accessibility and Nuclear Localization Effects on Hematopoietic Lineage FateF31HL144115 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI MARTIN, ERIC W · 2019 to 2020
$75k
NHLBI NIH HHS F31 HL144115NHLBI NIH HHS R01 HL157405NHLBI NIH HHS U01 HL143402NIAID NIH HHS R01 AI130131
6 · The paper itself

Abstract

Cerebral malaria (CM) from Plasmodium falciparum is a major cause of death in African children. Since bradykinin (BK) is a mediator of vasogenic edema, we hypothesized that it contributes to the pathogenesis of CM in Kenyan children and Plasmodium berghei ANKA-infected (PbA-infected) C57BL/6J mice in experimental CM (ECM). Cleaved plasma high-molecular-weight kininogen (cHK) is a marker for BK release. 40% of children with central nervous system malaria had plasma cHK versus 18% of children with uncomplicated malaria. Wild-type PbA-infected mice with ECM had circulating cHK, elevated BK levels, and reduced HK and prekallikrein activity/antigen levels. HK-null (Kng1-/-), combined BK B1- and B2 receptor-null (Bdkrb1-/-Bdkrb2-/-), BK B2 receptor-null (Bdkrb2-/-), or BK B1 receptor-null (Bdkrb1-/-) mice were protected significantly from neurologic deterioration and brain edema compared with wild-type mice. F12-/- mice were not protected from neurological deterioration. Prekallikrein-null (Klkb1-/-), prolylcarboxypeptidase hypomorph (Prcpgt/gt), and brain endothelial cell conditional KO of PRCP (Prcpfl/fl Cre) mice with ECM had reduced neurologic deterioration and brain edema. Adjuvant plasma kallikrein inhibition combined with artesunate treatment in PbA-infected mice reversed neurologic deterioration and brain edema and significantly prolonged survival over artesunate alone. BK-induced vasogenic edema contributes to human and murine CM.

Indexed as

BradykininBrain EdemaMalaria, CerebralAnimalsChildDisease Models, AnimalFemaleHumansKininogensMaleMiceMice, Inbred C57BLMice, KnockoutPlasmodium bergheiReceptor, Bradykinin B1Receptor, Bradykinin B2BradykininKininogensReceptor, Bradykinin B1Receptor, Bradykinin B2HematologyInfectious diseaseKininVascular biology

Identifiers

PMID42446942
PMCPMC13528921

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.