Evidence map›Paper›PMID 33206327›Full record

ArticleTranslational stroke research2021

Molecular Correlates of Hemorrhage and Edema Volumes Following Human Intracerebral Hemorrhage Implicate Inflammation, Autophagy, mRNA Splicing, and T Cell Receptor Signaling.

Marc Durocher, Bodie Knepp, Alan Yee, Glen Jickling, Fernando Rodriguez, Kwan Ng, Xinhua Zhan, Farah Hamade, Eva Ferino, Hajar Amini and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational stroke research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Observational
  6. Molecular heterogeneity in human stroke - What can we learn from the peripheral blood transcriptome?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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  18. CD4Science advances · 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

15 authors at 3 institutions in 2 countries.

Marc Durocher *Department of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Bodie Knepp *Department of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Alan YeeDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Glen JicklingDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Fernando RodriguezDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Kwan NgDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Xinhua ZhanDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Farah HamadeDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Eva FerinoDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Hajar AminiDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Paulina Carmona-MoraDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Heather HullDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Bradley P AnderDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Frank R SharpDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
Boryana StamovaDepartment of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA. bsstamova@ucdavis.edu.ORCID 0000-0002-5440-8816
University of California, Davis · USUniversity of Alberta · CAUniversity of California System · US

Funding

Molecular Biology of Stroke in HumansR01NS075035 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R · 2012 to 2016
$3.1M
Genomics of Intracerebral Hemorrhage and its CausesR01NS106950 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ANDER, BRADLEY PEARCE, SHARP, FRANK R · 2019 to 2023
$3.0M
Whole Genome RNA Sequencing (RNAseq) of Blood from Patients with Lacunar StrokeR01NS101718 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R, STAMOVA, BORYANA · 2017 to 2021
$3.0M
Whole Transcriptome Studies of Patients with Transient Ischemic Attacks (TIAs)R01NS097000 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R, STAMOVA, BORYANA · 2016 to 2020
$2.8M
NINDS NIH HHS R01NS075035NINDS NIH HHS R01NS097000NINDS NIH HHS R01 NS101718NINDS NIH HHS R01NS106950
6 · The paper itself

Abstract

Intracerebral hemorrhage (ICH) and perihematomal edema (PHE) volumes are major determinants of ICH outcomes as is the immune system which plays a significant role in damage and repair. Thus, we performed whole-transcriptome analyses of 18 ICH patients to delineate peripheral blood genes and networks associated with ICH volume, absolute perihematomal edema (aPHE) volume, and relative PHE (aPHE/ICH; rPHE). We found 440, 266, and 391 genes correlated with ICH and aPHE volumes and rPHE, respectively (p < 0.005, partial-correlation > |0.6|). These mainly represented inflammatory pathways including NF-κB, TREM1, and Neuroinflammation Signaling-most activated with larger volumes. Weighted Gene Co-Expression Network Analysis identified seven modules significantly correlated with these measures (p < 0.05). Most modules were enriched in neutrophil, monocyte, erythroblast, and/or T cell-specific genes. Autophagy, apoptosis, HIF-1α, inflammatory and neuroinflammatory response (including Toll-like receptors), cell adhesion (including MMP9), platelet activation, T cell receptor signaling, and mRNA splicing were represented in these modules (FDR p < 0.05). Module hub genes, potential master regulators, were enriched in neutrophil-specific genes in three modules. Hub genes included NCF2, NCF4, STX3, and CSF3R, and involved immune response, autophagy, and neutrophil chemotaxis. One module that correlated negatively with ICH volume correlated positively with rPHE. Its genes and hubs were enriched in T cell-specific genes including hubs LCK and ITK, Src family tyrosine kinases whose modulation improved outcomes and reduced BBB dysfunction following experimental ICH. This study uncovers molecular underpinnings associated with ICH and PHE volumes and pathophysiology in human ICH, where knowledge is scarce. The identified pathways and hub genes may represent novel therapeutic targets.

Indexed as

Brain EdemaNeuroinflammatory DiseasesAutophagyCerebral HemorrhageEdemaHumansInflammationReceptors, Antigen, T-CellRNA, MessengerTomography, X-Ray ComputedReceptors, Antigen, T-CellRNA, MessengerGene expressionHematoma clearanceInflammationIntracerebral hemorrhage volumePerihematomal edema volumeVolume

Identifiers

PMID33206327
PMCPMC8421315
OpenAlexW3101516647

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.