# Mechanisms of capillary-associated microglial interactions

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $201,875

## Abstract

Project Summary
The brain requires a significant amount of energy compared to other organs. This high energy demand is met
by a dense network of blood vessel that deliver oxygen and nutrients and facilitates the removal of waste
products. Therefore, the interactions between the neurovasculature and brain cells are important. While
extensive work has been done to elucidate contributions by astrocytes and pericytes to vascular integrity, less
work has been done to understand microglial interactions with the vasculature.
Multiple lines of evidence suggest that microglia facilitate the development of the vasculature early in life and
following injury or in disease. However, the extent of microglial interactions with the vasculature in
homeostasis has not been adequately clarified. As resident immune cells, microglia are the brain’s first line of
defense and it is possible that they could help detect pathogens or abnormalities in the circulation, but this
would perhaps require stable physical interactions with the vasculature. In our preliminary studies for this
project, we used in vivo two photon and electron microscopy approaches to document robust physical
interactions between a subpopulation of microglial somata and the microvasculature (capillaries) across brain
regions and brain age. Remarkably, even with pharmacological elimination and subsequent repopulation of
microglia, the density of these capillary-associated microglia (CAM) was maintained suggesting that capillary
association is a critical feature of microglial residence in the brain. In our proposed studies, we will: (1)
attempt to differentiate CAMs from parenchymal microglia by using morphological, functional and
transcriptional approaches; and (2) test the hypothesis that CAM interactions are facilitated by purine release
from endothelial pannexins that recruit microglia through P2Y12 receptor sensing. This project is a first to
thoroughly characterize capillary associated microglia and elucidate salient molecular mechanisms governing
these interactions to understand microglia-vascular interactions in homeostasis.

## Key facts

- **NIH application ID:** 10241550
- **Project number:** 5R21NS119727-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ukpong Bassey Eyo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241550

## Citation

> US National Institutes of Health, RePORTER application 10241550, Mechanisms of capillary-associated microglial interactions (5R21NS119727-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241550. Licensed CC0.

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