# Sex differences in traumatic brain injury: Neural circuit mediators of overlapping stress and physical effects

> **NIH NIH F32** · EMORY UNIVERSITY · 2023 · $76,080

## Abstract

PROJECT SUMMARY
Women experience worse symptoms and outcomes following traumatic brain injury (TBI), contrary to the
consensus in preclinical research that female sex hormones confer neuroprotection. Multiple mechanisms
have been proposed to drive this health disparity, including hormonal fluctuations during the menstrual cycle
and into the menopausal transition, a predisposition to seek medical attention or report symptoms, and
increased neurobiological vulnerability to injury. In particular, increased vulnerability to mechanical trauma in
female axons and the role of neurosteroid hormones have not been thoroughly examined in human TBI.
While mild traumatic brain injuries (mTBI) make up the majority of TBIs, research often focuses on a specific
sub-type of mTBI: sports-related concussions. However, many people experience head trauma during a
traumatic event, such as motor vehicle collisions, physical assault, sexual assault, or falls, and the lifetime
prevalence of experiencing at least traumatic event is extremely high (90%). As the literature on sports-related
concussions may not always generalize to this trauma-exposed population, we aim to characterize sex
differences in structural and functional connectivity (Aim 1), examine sex-dependent associations between TBI
pathophysiology and outcomes (Aim 2), and finally assess the influence of concurrent estradiol levels on TBI
outcomes and neuroimaging markers (Aim 3) To address these aims, I will leverage a large, existing dataset
from the AURORA study, a multisite, longitudinal study of posttraumatic outcomes. Participants were recruited
to AURORA if they presented to a participating Emergency Department (ED) within 72 hours of a qualifying
traumatic event and then were followed through 12-months posttrauma. Participants were assessed using a
multidimensional range of tools and measures to general a one-of-a-kind, rich dataset to study the complex,
co-occurring symptoms and overlapping neural correlates of adverse posttraumatic neuropsychiatric sequelae
across a variety of disciplines. About one-third of AURORA participants met modified American Congress of
Rehabilitation Medicine criteria for TBI. However, as the acute and chronic stress responses can mask and
compound signs and symptoms of TBI, it is essential to use an objective marker to establish TBI in this trauma-
exposed cohort. We propose to use ED GFAP levels to identify individuals with TBI, which have shown to be
significantly elevated in individuals with TBI for several days following presentation at the ED. TBI outcomes
will include not only somatic symptoms (e.g., headache, sensitivity to light) but also PTSD and depression
symptoms and mental health-related quality of life. Completion of this project will not only inform our
understanding of neurobiological factors that affect sex differences in TBI outcomes but also provide excellent
postdoctoral training for the applicant in diffusion magnetic resonance imaging, resting-state f...

## Key facts

- **NIH application ID:** 10751089
- **Project number:** 1F32MH134528-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Megan E Huibregtse
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,080
- **Award type:** 1
- **Project period:** 2023-07-14 → 2025-07-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751089

## Citation

> US National Institutes of Health, RePORTER application 10751089, Sex differences in traumatic brain injury: Neural circuit mediators of overlapping stress and physical effects (1F32MH134528-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10751089. Licensed CC0.

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