Evidence map›Paper›PMID 41828358›Full record

ArticleInternational journal of molecular sciences2026

Extracellular Histones Associate with Blood-Brain Barrier Disruption and Astrocyte-Mediated Neuroinflammation During Polymicrobial Sepsis.

Fatemeh Fattahi, Jamison J Grailer, Elizabeth A Malan, Michella Parlett, Firas S Zetoune, Guowu Bian, Matthew J Delano, Svetlana M Stamatovic, Anuska V Andjelkovic, Peter A Ward

Abstract read
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In one paragraph

Article in International journal of molecular sciences, 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

10 authors.

Fatemeh FattahiDivision of Allergy and Clinical Immunology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jamison J GrailerDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-6604-6819
Elizabeth A MalanDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Michella ParlettDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Firas S ZetouneDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Guowu BianDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Matthew J DelanoDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Svetlana M StamatovicDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Anuska V AndjelkovicDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Peter A WardDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0003-1285-8365

Funding

NIH Common Fund NIA R56AG61207NIH Common Fund NIGMS R01GM29507NIH Common Fund NIGMS R01GM61656
6 · The paper itself

Abstract

Histones, normally confined to nucleosomes, are released into the bloodstream during sepsis due to cell damage and NETosis, contributing to organ dysfunction. In sepsis-associated encephalopathy (SAE), histones may worsen neurological outcomes. Using a cecal ligation and puncture (CLP)-induced polymicrobial sepsis model, we evaluated histone release, blood-brain barrier (BBB) disruption, complement activation, and glial responses in the brain. Immunofluorescence revealed histone accumulation and increased soluble histone levels in the brain 8-24 h post-CLP. BBB permeability increased, confirmed by FITC-inulin and Texas Red-dextran clearance assays. Complement activation, along with increased GFAP-positive astrocytes and Iba1-positive microglia, occurred post-CLP. Histones were detected in astrocytes and microglia. In vitro, stimulated astrocytes released histones upon activation and also demonstrated the ability to uptake extracellular FITC-labeled histones. Histone exposure elevated intracellular calcium levels and triggered cytokine secretion in astrocytes. Notably, histone stimulation activated the NLRP3 inflammasome, amplifying inflammation. These findings suggest that histone release during sepsis drives neuroinflammation, BBB disruption, and glial activation, positioning extracellular histones as potential therapeutic targets for sepsis-related brain manifestations like SAE.

Indexed as

AstrocytesBlood-Brain BarrierHistonesNeuroinflammatory DiseasesSepsisAnimalsDisease Models, AnimalMaleMiceMicrogliaSepsis-Associated EncephalopathyHistonesblood–brain barrier (BBB) permeabilityglial fibrillary acidic protein (GFAP)neutrophil extracellular traps (NETs)sepsis-associated encephalopathy (SAE)

Identifiers

PMID41828358
PMCPMC12985147

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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.