# Traumatic Brain Injury and Vascular Disease

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Objective: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the veteran population.
In the United States, there are an estimated 5.3 million people living with a TBI-related disability. TBI
commonly leads to neurocognitive deficits, however, other systemic effects have also been associated with
TBI. Cardiovascular effects include stress-related cardiomyopathy, arrhythmias, ECG repolarization changes,
and increased cardiac reactive oxygen species. These effects may be mediated by catecholamine surges,
although the mechanism(s) are unclear. In a clinical study of TBI in US veterans, TBI was strongly associated
with the severity of coronary artery calcification as measured by electron beam computed tomography,
suggesting TBI may promote processes involved in atherogenesis. Importantly, there was a marked
independent association of TBI with cardiovascular mortality with a relative risk of 2.89 compared to a non-TBI
control group, even after adjusting for typical cardiovascular risk factors. These observations indicate there
may be a chronic and potent effect of TBI on atherosclerosis. However, whether these findings represent a
direct link between TBI and systemic vascular changes or represent other confounding factors is unclear. The
goal of this application is to determine the impact of TBI on vascular disease and to uncover underlying
mechanisms responsible for these effects. Based on these results, therapeutic interventions will be tested in
attempts to block the vasculopathic effects of TBI.
Research Plan: To assess the effect of TBI in vascular disease processes, mouse models of TBI will be used
to determine the effects of brain injury on sympathetic activity, vascular function, leukocyte-endothelial
interactions and the development of atherosclerosis. Biomarkers and possible mediators will be measured
through a combination of flow cytometry, liquid chromatography with tandem mass spectrometry, ELISA’s,
magnetic resonance imaging, and histological analyses. Therapies designed to block activation of candidate
adrenergic and downstream cytokine-triggered inflammatory pathways following TBI will be tested using
relevant vascular endpoints.
Methods: The strategy to accomplish the objectives will be to use in vivo mouse models, ex vivo, and in vitro
assays to explore mediators of inflammation and vascular disease associated with TBI. Aim 1 will determine
the effect of TBI on leukocyte-endothelial interactions and vascular function in atherosclerotic-prone
mice.These endpoints will shed light on mechanisms related to the increased vascular risk associated with TBI.
Aim 2 will explore mechanism(s) by which TBI promotes atherosclerosis by characterizing inflammatory
responses, measuring catecholamines, and testing effects of adrenergic antagonists on vascular endpoints.
Aim 3 will determine the role of downstream mediators, p-selecting glyocoprotein ligand-1, interleukin-1
receptor, and neutrophil extracellular traps (NETs) ...

## Key facts

- **NIH application ID:** 10121811
- **Project number:** 1I01BX004836-01A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Daniel T Eitzman
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121811

## Citation

> US National Institutes of Health, RePORTER application 10121811, Traumatic Brain Injury and Vascular Disease (1I01BX004836-01A2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10121811. Licensed CC0.

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