# Chronic behavioral outcome and neuroinflammatory consequences of TBI

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $81,021

## Abstract

ABSTRACT
Neuroinflammation has emerged as a critical component of secondary injury following brain trauma. Recent pre-
clinical studies have shed light on the neurotoxic effects of peripheral-derived monocyte/macrophages (PDM).
Our preliminary findings suggest this response may be dampened in the presence of juvenile-derived murine
PDMs, however the cause of this neuroprotective response remains unknown. The research objective of this
application is to characterize the cellular and molecular mechanism(s) underlying the divergent, age-dependent
PDM response and their role in mediating neurovascular dysfunction following TBI. Our proposal builds upon
extensive preliminary and published data demonstrating a distinct age-at-injury response following TBI. Juvenile-
derived PDMs display reduced pro-inflammatory phenotype, and adult PDM depletion and replacement with
those from juvenile mice confer neuroprotection. Moreover, we discovered that PDM-specific Tie2/EphA4
receptor crosstalk regulates their pro-inflammatory state across the age spectrum. We hypothesize that age-
related differences in the PDM response underlie divergent outcomes following TBI. We will employ cell-specific
depletions, and PDM replacement as well as novel transgenic murine models. These approaches will include
rigorous behavioral, histological and innovative low-input genome-wide omics assessment of the relevance and
mechanism(s) of PDM age on injury outcomes. We will also provide a framework for retooling the
neuroinflammatory response to accelerate pro-recovery and dampen pro-inflammatory processes after TBI.

## Key facts

- **NIH application ID:** 11089780
- **Project number:** 3R01NS119540-04S1
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Michelle Lee Theus
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $81,021
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089780

## Citation

> US National Institutes of Health, RePORTER application 11089780, Chronic behavioral outcome and neuroinflammatory consequences of TBI (3R01NS119540-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11089780. Licensed CC0.

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