Related Experiment Video
Updated: Sep 13, 2025
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis
Ruchita Kothari1, Mostafa W Abdulrahim2, Hyun Jong Oh1
1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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.
Insights
Mast cells in the brain
Area of Science:
- Neuroimmunology
- Inflammation Biology
- Stroke Research
Background:
- The brain's immune environment is crucial for injury response.
- Ischemic stroke disrupts this balance, causing unclear inflammatory mechanisms.
Purpose of the Study:
- To elucidate the mechanism of post-stroke brain inflammation.
- To identify key regulators of immune cell migration into the brain.
Main Methods:
- Investigated the role of mast cell receptor Mrgprb2 in a mouse stroke model.
- Analyzed mast cell degranulation, neutrophil recruitment, and semaphorin 3a cleavage.
- Examined human MRGPRX2 expression and activation by substance P.
Main Results:
- Mrgprb2 mediates meningeal mast cell degranulation post-stroke.
- This recruits neutrophils from skull bone marrow into the brain via dura mater.
- Inhibition of Mrgprb2 reduced inflammation and improved outcomes in mice.
Conclusions:
- Mrgprb2 acts as a meningeal gatekeeper controlling immune cell entry into the brain after stroke.
- MRGPRX2 is the human ortholog, activated by substance P.
- Targeting Mrgprb2 offers a potential therapeutic strategy for stroke.
