# Effect of Mild TBI on Female Mice with a Controlled Estrous Cycle

> **NIH NIH R03** · ROSKAMP INSTITUTE, INC. · 2020 · $162,000

## Abstract

Abstract
Traumatic brain injury (TBI) is a complex condition with many variables within the human
population, both with the parameters of the injury and in the demographics of those affected by
it. Some studies have found a neuroprotective effect of female sex hormones, but attempts to
translate these findings into human clinical trials have failed. Most pre-clinical TBI studies focus
on male animals in order to eliminate variability induced by cycling levels of sex hormones in
female animals. The influence of endogenous sex hormone levels on the outcome from TBI is
under-studied, particularly within mild TBI (mTBI). Few studies have examined the influence of
the estrous cycle by administering injuries at controlled points, and given the high proportion of
mTBI within the human TBI population, it is important to understand the effect this may have on
the outcome from TBI. Improving our understanding will also inform both past and future pre-
clinical experiments that involve a mix of male and female animals.
Our group has extensive experience modeling mild TBI in mice, and in our previous studies we
have found significant sex-dependent differences in the neurobehavioral and pathological
outcomes acutely after TBI. In this study we propose to use the Lee-Boot effect on group
housed female mice to produce a prolonged diestrus phase where endogenous levels of
progesterone and estradiol are low. The Whitten effect will be used on a separate cohort of
group housed females where they will be exposed to male pheromones in their bedding to
stimulate a normal estrous cycle. This cohort will be injured at the proestrus phase when
progesterone and estradiol levels are high. Male mice will also be included along with sham
control mice. Tail vein blood draws will take place at the time of injury in order to quantify
endogenous hormone levels. The motor performance and memory of the animals will be tested
for two weeks following injury and the pathological outcome will be examined at that time using
markers for neuroinflammation, axonal injury and white matter loss.
Correlating the endogenous hormone levels to neurobehavioral and pathological outcome from
TBI at controlled points in the estrous cycle will provide valuable information on the role of
estrous cycle fluctuations in modulating outcome. If elevated levels of endogenous
progesterone and estradiol do alter the outcome from TBI it will be important to understand how
they may interact with treatment studies before proceeding with future human clinical trials.

## Key facts

- **NIH application ID:** 9875916
- **Project number:** 1R03NS115019-01
- **Recipient organization:** ROSKAMP INSTITUTE, INC.
- **Principal Investigator:** Scott Allen Ferguson
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,000
- **Award type:** 1
- **Project period:** 2019-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875916

## Citation

> US National Institutes of Health, RePORTER application 9875916, Effect of Mild TBI on Female Mice with a Controlled Estrous Cycle (1R03NS115019-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9875916. Licensed CC0.

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