Evidence map›Paper›PMID 34983246›Full record

ArticleStroke2022

Regulatory T Cells Contribute to Sexual Dimorphism in Neonatal Hypoxic-Ischemic Brain Injury.

Lucia Beckmann, Stefanie Obst, Nicole Labusek, Hanna Abberger, Christian Köster, Ludger Klein-Hitpass, Sven Schumann, Christoph Kleinschnitz, Dirk M Hermann, Ursula Felderhoff-Müser and 3 more

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

Article in Stroke, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
13.7field-weighted citation impact, top 1% 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

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.

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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

13 authors at 3 institutions in 1 country.

Lucia Beckmann *Department of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Stefanie Obst *Department of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.ORCID 0000-0002-9797-1262
Nicole Labusek *Department of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.ORCID 0000-0002-1978-6176
Hanna AbbergerInstitute of Medical Microbiology, Molecular Infection Immunology (H.A., W.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Christian KösterDepartment of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Ludger Klein-HitpassInstitute of Cell Biology, Genomic and Transcriptomic Facility (GTF) (L.K.-H.), University Hospital Essen, University Duisburg-Essen, Germany.ORCID 0000-0002-6406-8376
Sven SchumannInstitute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany (S.S.).
Christoph KleinschnitzCenter for Translational Neuro- and Behavioral Sciences (C-TNBS) (L.B., S.O., N.L., C. Köster, C. Kleinschnitz, D.M.H., U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Dirk M HermannCenter for Translational Neuro- and Behavioral Sciences (C-TNBS) (L.B., S.O., N.L., C. Köster, C. Kleinschnitz, D.M.H., U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Ursula Felderhoff-MüserDepartment of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Ivo BendixDepartment of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.ORCID 0000-0002-9751-3640
Wiebke HansenInstitute of Medical Microbiology, Molecular Infection Immunology (H.A., W.H.), University Hospital Essen, University Duisburg-Essen, Germany.
Josephine HerzDepartment of Pediatrics I, Neonatology & Experimental Perinatal Neurosciences (L.B., S.O., N.L., C. Köster, U.F.-M., I.B., J.H.), University Hospital Essen, University Duisburg-Essen, Germany.
University of Duisburg-Essen · DEEssen University Hospital · DEJohannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeNeonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of death and disability in newborns. Clinical and experimental studies suggest a sexual dimorphism in HI-induced brain injury and therapy responses. A major hallmark of HI pathophysiology is the infiltration of peripheral immune cells into the injured brain. However, the specific role of regulatory T cells (Tregs) in neonatal HI is still unknown.

methodsNine-day-old mice were exposed to HI by ligation of the right common carotid artery followed by 1 hour hypoxia (10% oxygen). Using immunohistochemistry, flow cytometry, and microarray analyses, Tregs were investigated in the brain, spleen, and blood 24 hours post HI. The functional role of Tregs was evaluated by acute Treg depletion in depletion of regulatory T cells transgenic mice. Brain injury, neuroinflammatory responses, and vascular injury were analyzed via immunohistochemistry and Western blot 48 hours and 7 days after HI. Functional outcome was assessed 3 days and 5 weeks after HI.

resultsFemale mice revealed an increased cerebral Treg infiltration, coinciding with elevated chemokine receptor expression. Treg depletion in females aggravated HI-induced brain tissue injury, short-term motor deficits, and long-term deficits in exploratory activity, paralleled by an increased microglia and endothelial activation and leukocyte infiltration. Treg depletion in male mice reduced HI-induced brain injury, short-term motor, and long-term cognitive deficits, associated with reduced vascular injury. Ex vivo isolated female Tregs displayed an increased immunosuppressive activity on effector T cell proliferation and an increased gene enrichment in pathways related to enhanced Treg activity.

conclusionsTregs from neonatal female mice provide endogenous neuroprotection, whereas Tregs from male mice increase secondary neurodegeneration. As potential mechanisms, we identified intrinsic transcriptional differences associated with enhanced anti-inflammatory activity of female Tregs. Our study emphasizes the urgent need for sex-stratified clinical and preclinical analyses.

Indexed as

AnimalsAnimals, NewbornBehavior, AnimalBrainCerebrovascular DisordersCognition DisordersFemaleHypoxia-Ischemia, BrainMaleMiceMice, Inbred C57BLMice, TransgenicMovement DisordersNeuroinflammatory DiseasesNeuronsPregnancybrainhypoxiaischemiaregulatory T cellssex-difference

Identifiers

PMID34983246
PMCPMC8785522
OpenAlexW4206582626

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.