# Mrgprb2 mediated neuroinflammation after cerebral ischemia

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2024 · $199,480

## Abstract

ABSTRACT
I am finishing my cerebrovascular fellowship in the department of neurosurgery at the Johns Hopkins School of
Medicine, where I will start as an assistant professor of neurosurgery with a practice focused on cerebrovascular
diseases. I am applying for a mentored surgeon-scientist career development award (CDA) to obtain further
training in neuroscience, immunology, and animal models of cerebral ischemia. This will further my long-term
career goals of exploring neuro-immunologic mechanisms underlying cerebral ischemia, and hopefully provide
a basis for new investigations in patients experiencing ischemic stroke.
 A major mechanism underlying stroke pathology involves neuroinflammation, where activation of
microglia and infiltration of peripheral leukocytes worsen neuronal injury and cell death. Despite substantial pre-
clinical efforts, there exists no efficacious therapeutic in limiting post-stroke neuroinflammatory damage. Mast
cells are tissue specific, long-lived immunologic effector cells which are thought to be one of the first-responders
in immune surveillance and activation, activating multiple pathways of the innate immune system. As such, the
ability to suppress mast cell activation may broadly attenuate multiple pathways of cerebral inflammation after
stroke. Recently, Mrgprb2 was identified as a mast cell-specific G-coupled protein receptor for basic
secretagogues, mediating IgE-independent activation. I have shown preliminarily that deletion of Mrgprb2 results
in decreased stroke volume after transient middle cerebral artery occlusion (tMCAO), with decreased
transcription and production of TNFa and CCL2 after stroke, and decreased neutrophil recruitment into the
ischemic brain. This CDA proposes building upon my pharmacology graduate training in mechanisms of cell
death and cocaine addiction, towards a new direction at the interface of neuroscience and immunology. I hope
this CDA will allow me to receive multidisciplinary training in the Departments of Neuroscience and Cellular and
Molecular Medicine. Specific training goals include: (1) Training in advanced basic neuroscience techniques
including dural and meningeal microdissection, and in-vivo live-animal imaging (2) Training in animal models
of cerebral ischemia including photo-thrombotic stroke (3) Didactic and experimental training in immunology
and neuro-immune interactions (4) Additional training in the ethical and responsible conduct of research.
 The research plan seeks to address the hypothesis that Mrgprb2 is a critical mast cell specific receptor
which upregulates the initial immunologic activation response after cerebral ischemia, and that inhibition of the
physiologic ligand for Mrgprb2 may decrease neuroinflammation after stroke. The Specific Aims of the proposal
are to: (1) Investigate which subset of mast cell mediators are regulated by Mrgprb2 in ischemic stroke (2)
Determine the localization and expression pattern of Mrgprb2 in central nervous system mast c...

## Key facts

- **NIH application ID:** 10836014
- **Project number:** 5K08NS131599-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RISHENG XU
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $199,480
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836014

## Citation

> US National Institutes of Health, RePORTER application 10836014, Mrgprb2 mediated neuroinflammation after cerebral ischemia (5K08NS131599-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836014. Licensed CC0.

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