# Understanding the immune response after mild TBI: Do endothelial cells play a major role?

> **NIH NIH F31** · UNIVERSITY OF KENTUCKY · 2021 · $41,647

## Abstract

PROJECT SUMMARY/ABSTRACT:
The vast majority (over 90%) of traumatic brain injuries (TBI) are classified as mild TBI (mTBI). While most
individuals recover from mTBI quickly, a significant minority (10-15%) of patients with mTBI experience
persistent symptoms – there are no FDA approved treatments for these individuals. Chronic neuroinflammation
and vascular disruption following TBI create an unfavorable environment for recovery. More broadly,
neuroinflammation and vascular dysfunction are significant contributors to other CNS diseases as well,
including Alzheimer’s disease. My preliminary results demonstrate that interleukin-1 (IL-1) signaling through
interleukin-1 receptor 1 (IL-1R1) may be as a link between chronic neuroinflammation and vascular pathology
and serve as a therapeutic avenue. IL-1, a major pro-inflammatory cytokine, is upregulated following all TBI
severities. IL-1 release has been linked with downstream alterations of the vasculature, including changes to
the neurovascular unit, blood flow alteration, angiogenesis, and increased release of cytokines, chemokines,
and growth factors. We have found that brain endothelial cells express a high number of IL-1R1 receptors.
Further, we have demonstrated that mice lacking IL-1R1 show reduced neuroinflammation following
experimental mTBI. We hypothesize that following mTBI, brain endothelial cells, specifically through IL-
1R1, act as a mediator of the neuroimmune and vascular responses. To test this hypothesis, we will use a
closed head injury model (CHI) to model a mTBI in mice. Further, we will manipulate IL-1R1 using an inducible
endothelial cell-specific IL-1R1 knockout (eKO), a global knockout in which IL-1R1 has been restored only in
the endothelial cells (eRestore), and an IL-1R1 reporter mouse in which the protein and mRNA are labeled. In
aim 1, we will determine the cellular and temporal expression changes of IL-1R1 in the brain following CHI
using the reporter mice. Through this aim, I will be able to determine how TBI alters IL-1R1 across time as well
as IL-1R1 association with arteries, veins, and capillaries, while also honing my skills in histology techniques.
In aim 2, we will delineate endothelial IL-1R1-dependent neuroinflammatory responses following CHI in
wildtype, eKO, and eRestore mice. Through this aim, I will get experience in animal surgeries as well as RNA
isolation and Nanostring gene expression analysis. Finally, in aim 3, we will investigate the involvement of
endothelial IL-1R1 in vascular structure and blood flow changes after TBI. To do this, we will use vessel
painting and speckle contrast diffusion correlated tomography (scDCT). If we find support for our hypothesis,
we will provide the groundwork for the development of IL-1 therapeutics for the treatment of mTBI, as well as
describe a physiological response of the CNS that can be applied to other diseases. Overall, the question
outlined in this proposal not only moves the field forward but also provides s...

## Key facts

- **NIH application ID:** 10227663
- **Project number:** 5F31NS116912-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Colleen Bodnar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,647
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227663

## Citation

> US National Institutes of Health, RePORTER application 10227663, Understanding the immune response after mild TBI: Do endothelial cells play a major role? (5F31NS116912-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227663. Licensed CC0.

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