# CTBI: Traumatic brain injury-induced inflammation effects on cognitive evaluations and response inhibition: Mechanisms of increased risk for suicidality

> **NIH VA I01** · VA NEW JERSEY HEALTH CARE SYSTEM · 2021 · —

## Abstract

This Merit proposal is part of a BLR&D Collaborative Merit Award for TBI (CTBI) proposal (RFP #BX-19-006)
involving three separate but integrated proposals that together investigate the mechanisms by which TBI
enhances impulsivity and suicidal behavior in Veterans. The rationale for the collaborative project is to combine
neurobiological mechanistic studies in animals with human imaging and biomarker analysis to understand the
manner in which TBI influences impulsivity and suicidal behavior. The overarching hypothesis is that TBI
enhances impulsivity, a risk factor for suicide particularly in response to stress, through inflammation and
dysfunction of the serotonin system and frontal lobe circuitry.
The number of new traumatic brain injury (TBI) cases for U.S. Military forces has more than doubled in the last
five years and will continue to grow. TBI is a risk factor for suicidality. Moreover, increased impulsivity is one
of the most prevalent symptoms following TBI, and is itself a risk factor for suicide, depression and drug abuse.
Thus, understanding the underlying mechanisms responsible for high impulsivity following TBI is key to
understanding the link between TBI and suicide. Serotonin is important for rational decision-making and loss
of serotonin neurons leads to increased impulsivity. Previously, we demonstrated that mild TBI (mTBI) in an
animal model caused long-lasting suppression of the acoustic startle response (ASR), pathological
inflammation and degeneration of neurons in the nucleus reticularis pontis caudalis (PnC), a brain region
essential for ASR. Anatomically, serotonergic neurons in the pontine raphe nucleus are located in the
immediate vicinity of the PnC, and it is not unreasonable to expect inflammation and neurodegeneration in the
raphe nucleus following mTBI, as in the PnC. Our preliminary data support this idea. We also present
preliminary results that mTBI increases motor and cognitive impulsivity following lateral fluid percussion injury
in rats. The proposed studies will build on these preliminary results and investigate the hypothesis that
inflammation and degeneration of the serotonergic raphe nuclei lead to increased impulsivity after TBI. This
hypothesis will be tested in three aims. Aim 1 will determine whether mild TBI (mTBI) alone and in
combination with social isolation stress enhances impulsivity. The lateral fluid percussion injury model will be
used to generate mTBI in rats. Two aspects of impulsivity will be assessed: motor impulsivity and cognitive
impulsivity using a Go/No-Go and a delay discounting procedure, respectively. It is predicted that impulsivity
will be increased at 1 month and continue to worsen at 3 months after TBI. Aim 2 will determine whether mTBI
causes inflammation and degeneration of serotonergic raphe neurons. The prediction is that mTBI will cause
an early inflammatory response in the raphe nuclei, followed by loss of serotonergic neurons starting at 1
month after mTBI with greater ...

## Key facts

- **NIH application ID:** 10076543
- **Project number:** 5I01BX004561-02
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Kevin D. Beck
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076543

## Citation

> US National Institutes of Health, RePORTER application 10076543, CTBI: Traumatic brain injury-induced inflammation effects on cognitive evaluations and response inhibition: Mechanisms of increased risk for suicidality (5I01BX004561-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10076543. Licensed CC0.

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