# Cardiovascular dysfunction following Traumatic Brain Injury

> **NIH VA IK2** · CLEMENT J. ZABLOCKI VA MEDICAL CENTER · 2024 · —

## Abstract

Every year more than 15,000 – 30,000 Veterans and service members suffer a traumatic brain injury (TBI)
according to the Department of Defense (DOD). Mortality from TBI is high and many survivors suffer from
reduced life expectancy and persistent disability, including post-traumatic stress disorder (PTSD), which might
be due to autonomic nervous system (ANS) dysfunction. ANS dysfunction can be quantified by reduced heart
rate variability (HRV) and baroreceptor reflex sensitivity (BRS), which are associated with poor neurological
outcomes, arrhythmias, and death. The proposed studies will assess TBI-impaired central neuronal circuitry to
address the overall hypothesis that TBI-induced dysautonomia is not only a prognostic biomarker, but also a
pathogenic element compromising Veteran's health. This proposal investigates the amygdala, a brain region that
is related to fear, anxiety and PTSD, as well as in behavioral pathology following TBI, but is under-studied in the
ANS dysfunction following TBI. The amygdala is of interest because it: 1) controls ANS responses in humans
and rodents; 2); is damaged in human TBI and animal models; and 3) contributes to fear and anxiety in humans
and rodents. This constellation of factors is critical for Veterans health.
 A novel, rotational TBI model, that is bioengineered to mimic human injury will be employed in male and
female rats. This TBI model induces behavioral and ANS deficits, and damages the amygdala. The proposed
studies will implement a multi-faceted approach to examine cardiovascular (CV) disturbances following TBI by
monitoring blood pressure (BP) via surgically implanted radiotelemetry units from which heart rate (HR) , HRV,
and BRS will be derived in awake freely moving male and female rats during: 1) inactive, resting states; 2)
pharmacological stressors that disturb CV homeostasis; 3) pharmacological and chemogenetic manipulation of
the amygdala; and 4) fear conditioning with correlation between amygdala-dependent behaviors and CV
parameters.
 Aim 1 will examine the role of the amygdala in dysautonomia after TBI using HRV and BRS in response to
pharmacological stressors (systemic phenylephrine and nitroprusside) and amygdala microinjections. The
basolateral (BLA) and central amygdala (CeA) will be targeted with gamma-aminobutyric acid (GABA) agonists
or antagonists because GABAergic neurons control amygdala outflow to behavioral circuits and CV centers.
 Aim 2 will assess chemogenetic manipulation of amygdala circuits on CV control. Excitatory or inhibitory
DREADDs (designer receptors exclusively activated by designer drugs) will be expressed in the amygdala. HRV
and BRS will be evaluated at rest and following BP changes due to pharmacological stressors with DREADD
ligand or vehicle to confirm amygdala neurons as a potential therapeutic target for ANS dysfunction after TBI.
 Aim 3 will quantify the relationship between amygdala mediated fear behaviors and ANS parameters
following TBI. Behaviors d...

## Key facts

- **NIH application ID:** 10874409
- **Project number:** 5IK2BX005600-03
- **Recipient organization:** CLEMENT J. ZABLOCKI VA MEDICAL CENTER
- **Principal Investigator:** Christopher Jon Roberts
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874409

## Citation

> US National Institutes of Health, RePORTER application 10874409, Cardiovascular dysfunction following Traumatic Brain Injury (5IK2BX005600-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10874409. Licensed CC0.

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