# Preventing TBI-Induced Chronic Functional Loss with a Neuroprotective Antioxidant

> **NIH VA I01** · VA NEW JERSEY HEALTH CARE SYSTEM · 2020 · —

## Abstract

It is very important to uncover therapeutic strategies to combat the chronic effects of traumatic brain injury
(TBI) because currently, there are no effective treatments to prevent these cognitive deficits. Unfortunately,
TBI is a very common affliction of military forces that have served in recent combat operations. At least 15% of
deployed personnel receive a TBI and the total number of such injuries has been estimated as high as
320,000. In the US alone it is estimated that at least 1.7 million people suffer a TBI each year and the
worldwide incidence is approximately 0.5% per year. The vast majority of TBIs experienced by military
personnel are classified as mild injuries, but these do result in significant, chronic effects.
We seek to demonstrate an effective treatment that could reduce or reverse the long-term cognitive
dysfunction that is produced by mild traumatic brain injury (TBI). Because these injuries involve multiple
effects, it is necessary to further characterize the treatment effects on the lasting dendritic and spine changes
induced by TBI and add to our knowledge of therapeutic changes that are possible so that TBI patients will
benefit. Over the past several years, our lab has discovered that an activator of an antioxidant transcription
factor, Nrf2, can be neuroprotective by regulating molecular mechanisms that are important to the health of
neurons. This has led us to formulate a hypothesis that treatment of mild traumatic brain injury with the Nrf2
activator will result in significant improvement on the connections between neurons, promote neuroprotective
intracellular pathways, and result in greatly enhanced long-term outcomes following TBI. We will test our
hypothesis with three specific aims: 1. Prevention of the chronic behavioral effects of mild closed head injury
by tBHQ treatment, 2. Improvement of persistent connectivity changes produced by tBHQ treatment after mild
TBIs, and 3. Identify molecular changes induced by the post TBI treatment that could influence long-term
function. We will examine changes to molecular and long-term cognitive function after mild TBI accomplished
by the closed head impact injury model in mice. We will use a well-established TBI model involving a closed
head injury model that does include rotation. We will treat injured and sham injured groups with either vehicle
or tBHQ. Behavioral tests will be conducted at 1, 6, and 12 months after injury. Brain samples will also be
collected and examined for dendritic complexity, spine density, and neuron numbers. Finally, levels of
neuropathological pathway markers will be examined at early and late (12 month) time points, all to study the
effects of the post-injury treatment. In this way we will answer several key questions about the treatment of the
long-term effects of mild traumatic brain injury, how the treatment will affect molecular events that have lasting
consequences after injury, what happens to dendritic complexity after treatment at leng...

## Key facts

- **NIH application ID:** 10174732
- **Project number:** 5I01RX001520-08
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Bruce A. Citron
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-07-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174732

## Citation

> US National Institutes of Health, RePORTER application 10174732, Preventing TBI-Induced Chronic Functional Loss with a Neuroprotective Antioxidant (5I01RX001520-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174732. Licensed CC0.

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