# Blast-induced TBI in the ferret: small brains, big opportunities

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $437,000

## Abstract

Project Summary/Abstract: Traumatic brain injury (TBI) afflicts approximately three million Americans every
year with a high rate of long-term neurocognitive and behavioral morbidity. The true incidence of TBI likely
approaches 10 million as many mild cases go unreported. It is now recognized that repetitive mild TBI, or
concussions, may lead to the insidious onset of TBI-related neurodegeneration, a process termed Chronic
Traumatic Encephalopathy (CTE) which is now linked to Alzheimer's Disease Related Dementias (ADRD). TBI
and CTE are of particular concern among athletes engaged in contact sports and military personnel exposed to
concussive injuries resulting from explosions. In fact, it has been estimated that roughly 15–20% of deployed
US military personnel have sustained a blast-related TBI. While rodent work has provided initial information on
the effects of blast injury and recovery, translation from rodents into human TBI patients has been
challenging secondary to the gross differences in brain anatomy and physiology. The human brain is
gyrencephalic, containing extensive sulci and gyri whereas the rodent brain is lissencephalic lacking
surface convolutions and containing a much lower volume of white matter. This is an important distinction
as the presence of gyri greatly influences the movement of the brain within the skull upon impact with greater
deformation in gyrencephalic brains as compared to lissencephalic brains. In addition, sulci and gyri influence
the points of maximum mechanical stress in the brain during angular acceleration. In lissencephalic brains the
smooth brain surface distributes stress fields uniformly while in a gyrencephalic brain maximal stress is
focused at the base of the sulci. In fact, this is the precise location where pathologic phosphorylated tau protein
is maximally distributed in human CTE cases. Thus, current rodent models are inadequate and lack biofidelity
with the human condition. In the current proposal, we aim to develop the ferret as a small mammalian model
system with a well gyrated brain specifically for the study of TBI-associated neurodegeneration. The
gyrated brain of the ferret model approximates the gross anatomy of the human brain much more closely
than rodent models while avoiding the high costs associated with larger animal models such as non-
human primates, canines and swine. Taken together, we hypothesize that a ferret model of repetitive,
mild, blast-induced TBI will recapitulate the initiation and progression of human CTE with a high degree of
biofidelity as compared to a standard mouse model. To test this hypothesis we will determine whether
ferrets exposed to sham, single blast, or repeated blast-induced TBI develop deficits in learning, memory, and
skill acquisition benchmarked to a standard mouse model. We will also correlate these neurocognitive findings
with neuroanatomic, neurometabolic, and neuropathologic outcomes using longitudinal
contrast-enhanced,3D-MRI, 18 F-FDG PET, an...

## Key facts

- **NIH application ID:** 10122404
- **Project number:** 1R21NS116638-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** STEVEN J SCHWULST
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122404

## Citation

> US National Institutes of Health, RePORTER application 10122404, Blast-induced TBI in the ferret: small brains, big opportunities (1R21NS116638-01A1). Retrieved via AI Analytics 2026-09-09 from https://api.ai-analytics.org/grant/nih/10122404. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*