Evidence map›Paper›PMID 42853458›Full record

ArticleActa neuropathologica2026

Histone neutralization protects the ischemic brain against the consequences of stroke-associated pneumonia.

Dongpei Yin, Anran Li, Ayan Mohamud Yusuf, Olga Shevchuk, Janine Gronewold, Stephanie Thiebes, Tobias Tertel, Chen Wang, Nina Hagemann, Yiqiao Zhang and 26 more

Abstract read
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Article in Acta neuropathologica, 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

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

36 authors.

Dongpei Yin *Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Anran Li *Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Ayan Mohamud YusufDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Olga ShevchukInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Janine GronewoldDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Stephanie ThiebesInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Tobias TertelInstitute of Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Chen WangDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Nina HagemannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Yiqiao ZhangDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Claudia GraserDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Humeyra TasDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Michael FleischerDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Britta KaltwasserDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Benedikt FrankDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Ali Ata TuzInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Vikramjeet SinghInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Devon SiemesInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Ekaterina PylaevaDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jadwiga JablonskaDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Bente SiebelsSection Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hartmut SchlüterSection Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jonas RaspeTranslational Pulmonology, Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany.
Michaela SchedelTranslational Pulmonology, Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany.
Yi LiuDepartment of Neurology, Central Hospital, Dalian University of Technology, Dalian, Liaoning, China.
Fengyan JinDepartment of Hematology, First Hospital of Jilin University, Changchun, Jilin, China.
Ertugrul KilicDepartment of Physiology, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
Bayram YilmazIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey.
Egor DzyubenkoDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jens MinnerupDepartment of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany.
Luisa KlotzDepartment of Neurology, University of Münster, Münster, Germany.
Bernd GiebelInstitute of Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Oliver SoehnleinDepartment of Experimental Pathology, University Hospital Münster, Münster, Germany.
Matthias GunzerInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Daniel R EngelInstitute of Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Dirk M HermannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. dirk.hermann@uk-essen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bacterial pneumonia aggravates ischemic stroke via mechanisms that still remain to be determined. In ischemic stroke patients, we show that stroke-associated pneumonia is associated with poor clinical outcome and long-term neutrophil deregulation. In mice exposed to transient middle cerebral artery occlusion (MCAO), experimental S. pneumoniae pneumonia induced at 3 days after stroke impaired neurological recovery and increased blood-brain barrier breakdown, brain neutrophil infiltrates, cerebral microvascular thrombosis, and progressive brain atrophy. The antibiotic amoxicillin only partially ameliorated pneumonia-associated neurological deficits and neutrophil infiltrates. Proteome analysis revealed that pneumonia induced a degranulation, platelet activation, and NETosis signature in peripheral blood neutrophils of MCAO mice, which was partly reversed by amoxicillin treatment. Subsequent studies showed that neutrophils were critical mediators of pneumonia-associated blood-brain barrier breakdown and microvascular thrombosis. Notably, administration of an antibody neutralizing extracellular histone proteins during pneumonia reduced ischemic injury, restored neurological recovery and prevented long-term brain atrophy in stroke-associated pneumonia mice. These protective effects were not observed after degradation of neutrophil extracellular traps by DNase-I, blockade of neutrophil extracellular trap formation by LDC7559 or myeloperoxidase inhibition by AZD4831, when these treatments were administered on occasion of pneumonia. This study identifies extracellular histones as key drivers of inflammatory brain injury and establishes histone neutralization as a strategy that protects against the deleterious effects of pneumonia after stroke.

Indexed as

Brain IschemiaHistonesIschemic StrokeStrokeAnimalsBlood-Brain BarrierBrainDisease Models, AnimalExtracellular TrapsInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLNeutrophilsHistonesExtracellular histone-H4/H2AIschemic strokeMicroglial activationMicrovascular thrombosisNeurological recoveryNeutrophil extracellular trapNeutrophils

Identifiers

PMID42853458

What Socratic 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 Socratic graph.