Evidence map›Paper›PMID 41782870›Full record

ArticleFrontiers in immunology2026

S100A8/A9 inhibition reduces splenic myelopoiesis and improves outcomes after stroke.

Hyun Ah Kim, Annas Al-Sharea, Hannah X Chu, Sung-Chun Tang, Samoda A Rupasinghe, Shenpeng R Zhang, Prabhakara R Nagareddy, Grant R Drummond, Thiruma V Arumugam, Andrew J Murphy and 2 more

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Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Review
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

12 authors.

Hyun Ah Kim *Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Annas Al-Sharea *Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Hannah X Chu *Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Sung-Chun TangStroke Center, Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Samoda A RupasingheCentre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Shenpeng R ZhangCentre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Prabhakara R NagareddyDepartment of Internal Medicine, Section of Cardiovascular Diseases, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma, OK, United States.
Grant R DrummondCentre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Thiruma V ArumugamCentre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Andrew J MurphyHaematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Christopher G SobeyCentre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC, Australia.
Man K S LeeHaematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Neutrophils are among the earliest immune cells to infiltrate the ischemic brain and contribute to secondary neuronal damage. The alarmin S100 calcium-binding protein A8/A9 (S100A8/A9), predominantly released by neutrophils, is upregulated during this process. Although the bone marrow is recognized as the principal site of neutrophil production via myelopoiesis, the role of the spleen as an immune-responsive organ remains incompletely understood. Methods: In this study, we employed a transient middle cerebral artery occlusion model in male C57Bl/6 mice and examined immune responses 24 hours post-stroke in the blood, bone marrow and spleen using flow cytometry. To understand the role of S100A8/A9 in modulating stroke-induced myelopoiesis, we administered a small molecule inhibitor of S100A8/A9, ABR-215757, before and after stroke. Human brain was examined immunohistochemically. Results: Analysis of human brain tissue (4 stroke patients, 2 controls) indicated the presence of neutrophils and S100A8/A9 in infarcted regions. Interestingly, we observed a marked increase in splenic neutrophils, accompanied by an expansion of myeloid progenitors, indicating activation of extramedullary myelopoiesis. Given our previous work showing that S100A8/A9 promotes myelopoiesis, we pharmacologically inhibited S100A8/A9 to determine if this would modulate stroke-induced myelopoiesis. Treatment with ABR-215757 led to reduced splenic myelopoiesis, reversed neutrophilia, enhanced forelimb grip strength, and a one-third reduction in infarct size at 24 hours post-stroke. Conclusion: These findings identify the spleen as a key contributor to neutrophil production following stroke and suggest that targeting S100A8/A9 may mitigate myeloid skewing and improve neurological recovery.

Indexed as

Calgranulin ACalgranulin BMyelopoiesisSpleenStrokeAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLNeutrophilsCalgranulin ACalgranulin BS100A9 protein, mouseABR-215757inflammationmiddle cerebral artery occlusionmyelopoiesisS100A8/A9stroke

Identifiers

PMID41782870
PMCPMC12953063

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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.