# Neutrophils and Monocytes in Pediatric Ischemic Stroke

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $418,019

## Abstract

PROJECT SUMMARY (Description)
Ischemic stroke affects around 1 in 1600 to 4000 births, has the highest incidence in neonates and infants (<
one year of age), and may cause neurological sequalae, including motor and cognitive deficits. Infection and
immune responses are a major risk factor for pediatric stroke, but no immune-directed therapies are available.
In fact, supportive measures remain the mainstay of pediatric stroke care, since the lytic treatment carries a
high in neonates with fragile cerebrovascular vessels. In this project, we will use a murine model of pediatric
stroke, with and without lipopolysaccharides (LPS)-sensitization, to test the pathological roles of neutrophils
and monocytes towards the development of immunomodulation therapies.
Aim 1: To clarify how immune cells breach the pial/glia limitans barrier in pediatric LPS/stroke. We will use flow
cytometry and single-cell RNA-Seq analysis to determine the compositions and transcriptome of immune cells
in the meninges after LPS/stroke, and test whether anti-MMP9 treatment prevents the neutrophil influx.
Aim 2: To test whether there are two waves of monocytic infiltrates with distinct functions in pediatric stroke. We
will use CCR2-CreER mice to track monocytic infiltrates and single-cell RNA-Seq analysis, as well as, block the
influx of monocytes at different stage after stroke to address this issue.
Aim 3: To determine what constitutes the meninges-incurred pathogenicity of neutrophils after pediatric
LPS/stroke. Our RNA-Seq results suggest that neutrophils acquire IL-36gamma, a novel family of the IL-1
family cytokine, in the meninges. We will validate these findings and test the benefits of anti-IL36R treatment.
Successful completion of this project will shed insights into the mechanisms of pediatric ischemic stroke and
whether neutrophil/monocyte-targeted immunomodulation therapies could provide better clinical management.

## Key facts

- **NIH application ID:** 10872234
- **Project number:** 5R01NS125788-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Chia-Yi Kuan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $418,019
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872234

## Citation

> US National Institutes of Health, RePORTER application 10872234, Neutrophils and Monocytes in Pediatric Ischemic Stroke (5R01NS125788-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10872234. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*