Evidence map›Paper›PMID 40712576›Full record

ArticleCell2025

A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis.

Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Review
  2. Developments in Mast Cell Research.The Journal of allergy and clinical immunology · 2026
    Review
  3. Review
  4. Article
  5. Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Review
  6. Article
  7. Article
  8. Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026
    Review
  9. Article
  10. MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  11. Article
  12. Article
  13. Stromal Cell-Mast Cell Communication Orchestrates Anti-Viral Immunity in the Meninges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Review
  15. 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

22 authors.

Ruchita KothariThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mostafa W AbdulrahimDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hyun Jong OhThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Daniel H CapuzziThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Collin B KilgoreThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sumil K NairDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yaowu ZhangDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nathachit LimjunyawongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sarbjit S SainiJohns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Jennifer E KimDepartment of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Justin M CaplanDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Fernanado L GonzalezDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Christopher M JacksonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chetan BettegowdaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Judy HuangDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bhanu P GaneshDepartment of Neurology, The University of Texas Health Science Center Houston, McGovern Medical School, Houston, TX 77030, USA.
Chunfeng TanDepartment of Neurology, The University of Texas Health Science Center Houston, McGovern Medical School, Houston, TX 77030, USA.
Raymond C KoehlerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rafael J TamargoDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Louise D McCulloughDepartment of Neurology, The University of Texas Health Science Center Houston, McGovern Medical School, Houston, TX 77030, USA.
Risheng XuDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: rxu4@jhmi.edu.
Xinzhong DongThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: xdong2@jhmi.edu.

Funding

Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Functional Analysis of Mrgpr Family in itch sensationR37NS054791 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Xinzhong Dong · 2022 to 2026
$2.9M
Mrgprb2 mediated neuroinflammation after cerebral ischemiaK08NS131599 · NINDS · JOHNS HOPKINS UNIVERSITY · PI RISHENG XU · 2023 to 2026
$798k
American Heart Association-American Stroke Association 23PRE1020354Howard Hughes Medical InstituteNIGMS NIH HHS T32 GM136577NINDS NIH HHS K08 NS131599NINDS NIH HHS R37 NS054791
6 · The paper itself

Abstract

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal mast cells and is activated by upregulation of the neuropeptide substance P following stroke. Pharmacologically inhibiting Mrgprb2 reduces post-stroke inflammation and improves neurological outcomes in mice, providing a druggable target. Collectively, our study identifies Mrgprb2 as a critical meningeal gatekeeper for immune migration from skull bone marrow reservoirs into the brain.

Indexed as

BrainDura MaterMast CellsReceptors, G-Protein-CoupledReceptors, NeuropeptideStrokeAnimalsCell DegranulationCell MovementFemaleHumansInflammationMaleMeningesMiceMice, Inbred C57BLReceptors, G-Protein-CoupledReceptors, NeuropeptideSubstance Pinflammationischemic strokemast cellmeningesMrgpr receptorsemaphorinskull bone marrowsubstance P

Identifiers

PMID40712576
PMCPMC12313293

What OpenQuestion holds

Textmetadata
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.