# Monocyte-Derived Microglia in Development and after Neonatal Brain Injury

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2024 · $201,875

## Abstract

PROJECT SUMMARY (Abstract)
Microglia were once thought derived exclusively from the early yolk sac progenitors, but recent studies raised
the possibility of monocyte-derived microglia in normal development and particularly after neonatal brain injury,
including stroke, hypoxia-ischemia (HI), and inflammation/LPS-sensitized HI (LPS/HI). However, the extent of
monocyte-derived microglia in normal development is unknown, and the roles of monocyte-derived pathologic
microglia partially defined. Better understanding of these issues may shed mechanistic insights and suggest
potential treatments of neonatal brain injury. We will address these issues in three specific aims.
In Aim 1, we will use CCR2-Cre mice crossed with R26R-EGFP mice to determine the extent and distributions
of CCR2+ monocyte-derived microglia in the brain.
In Aim 2, we will use PF-04136309 (IP) to inhibit the MCP1/CCR2-mediated chemoattraction or clodronate
liposomes (IV) to ablate the blood-borne monocytes to assess their potential benefits against the neonatal
LPS/HI brain injury.
In Aim 3, we will use tamoxifen-dosed CCR2-CreER; R26R-EGFP mice to isolate monocyte-derived microglia-
like cells in LPS/HI-injured brains for single-cell RNA-Seq to search for the potential effectors responsible for
delayed neurotoxicity and damage to the synaptic network.

## Key facts

- **NIH application ID:** 10816517
- **Project number:** 5R21HD109025-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Chia-Yi Kuan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816517

## Citation

> US National Institutes of Health, RePORTER application 10816517, Monocyte-Derived Microglia in Development and after Neonatal Brain Injury (5R21HD109025-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10816517. Licensed CC0.

---

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