# Satellite Microglia: Role in Maladaptive Network Remodeling after TBI

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $473,106

## Abstract

PROJECT SUMMARY
Microglia, the primary mediators of innate immune activation in the brain, are increasingly recognized as key
modulators of neuronal activity and excitability. There is growing evidence in many neurological diseases,
including traumatic brain injury (TBI), that prolonged activation of the innate immune system can impede repair
and promote disease, and it is not understood if or how microglia's impact on neuronal excitability might
contribute or protect. One interesting microglial subtype that may be critical in the monitoring and feedback of
neuronal excitability is the perineuronal satellite microglia. These microglia are juxtaposed to neurons with their
soma and processes entwined around the neuronal cell body. Our published and preliminary data in TBI show
a dramatic increase in the percentage of neurons with satellite microglia at both one week15, and several
months after TBI that is associated with network hyperexcitability and behavioral dysfunction with deficits in
reversal learning. However, our preliminary data indicate that satellite microglia suppress neuronal excitability,
in control mice, but lose this ability in chronic TBI with an associated decrease in expression of P2Y12
receptors. With this proposal, we will investigate the role of perineuronal satellite microglia and P2Y12 receptors
in neuronal, network and cognitive dysfunction after TBI. In aim 1, we will utilize transgenic mice that allow
identification of microglia and associated neuronal subtypes to establish cell type-specific interactions of
satellite microglia with neurons and the associated effect on neuronal function. In aim 2, we will test the
mechanistic role of P2Y12 signaling in satellite microglial-associated neuronal interaction and function, network
hyperexcitability and cognitive deficits after TBI. In aim 3, we will validate satellite microglial-neuronal
interactions, P2Y12R expression, function and microglial expression profiles in human tissue in the context of
TBI compared to our murine model. Results from these studies will yield an in-depth understanding of how
microglial-neuronal interactions contribute to changes in neuronal excitability after injury and will give insight
into therapeutic targets for TBI-induced circuit and cognitive dysfunction.

## Key facts

- **NIH application ID:** 10799482
- **Project number:** 1R01NS129609-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Amber L Nolan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $473,106
- **Award type:** 1
- **Project period:** 2023-12-15 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799482

## Citation

> US National Institutes of Health, RePORTER application 10799482, Satellite Microglia: Role in Maladaptive Network Remodeling after TBI (1R01NS129609-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10799482. Licensed CC0.

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