# Mast Cell Signaling Connects the Brain and the Gut Post-Stroke

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $428,500

## Abstract

PROJECT SUMMARY / ABSTRACT:
Post-stroke inflammation (PSI) is a critical determinant of damage and recovery after stroke.
Increasing evidence suggests that peripheral inflammatory responses to stroke have an important
role in determining neurological outcome. Many inflammatory processes are activated by
ischemic stroke and lead to further damage. Mast cells (MCs) release large quantities of
histamine (HA), a pro-inflammatory transmitter that enhances inflammation and contributes to
neuronal death. HA-signaling after stroke in peripheral organs such as the gut, one of the major
sources of HA, have not been explored. The importance of the "BRAIN-GUT AXIS" in response
to stroke is increasingly recognized. Stroke elicits a vicious cycle of central and peripheral
inflammation through bi-directional communication within the "gut-brain axis". Maintaining the
integrity of gut barrier function is of utmost importance to prevent bacterial translocation and
sepsis, a leading cause of mortality in elderly stroke patients.
Histamine release and gut MCs (gMC) activation leads to severe gut inflammation. My
preliminary findings, which forms the foundation of this proposal, implicates stroke-induced gut
HA receptor activation as a key mediator of "brain-gut axis" communication after stroke. However,
the timing and of gut HA-signaling after stroke, and the potential to manipulate this axis to improve
functional recovery has not been investigated. Stroke induced a histamine spike in the blood that
was significantly and persistently elevated in aged versus young mice. We hypothesize that this
is secondary to activation of mast cells in the gut. Inhibition of HA-signaling in the peripheral
gut mucosa will lead to a suppression of both peripheral and brain inflammation, and improve
functional recovery and reduce mortality in an animal model of stroke. I will test the central
hypothesis that neuroinflammation results from elevated peripheral gut histamine signaling, MC
degranulation, gut barrier breakdown, loss of bacterial containment and trafficking of pro-
inflammatory mast cells to the brain. This will be more profound in aged mice. Aged MCs are
known to be in an increased state of activation with higher levels of histamine. Thus, aging is a
primary factor influencing the levels of HA. Given that aging is accompanied by chronic low-level
inflammation and is a non-modifiable risk factor for stroke, I will use aged (Ag) mice to study the
role of gMC-mediated histamine signaling in PSI. Preliminary data suggests that suppressing
histamine receptor (HR) activation and controlling HA release in the periphery post-stroke
improves outcomes. This R21 will investigate the molecular mechanisms underlying MC and HR
activation in the gut as a potential therapeutic target for better recovery after stroke.

## Key facts

- **NIH application ID:** 10058042
- **Project number:** 1R21NS114768-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Bhanu Priya Ganesh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $428,500
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058042

## Citation

> US National Institutes of Health, RePORTER application 10058042, Mast Cell Signaling Connects the Brain and the Gut Post-Stroke (1R21NS114768-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10058042. Licensed CC0.

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