# Tissue Softening in Traumatic Brain Injury

> **NIH NIH R03** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $74,878

## Abstract

Traumatic brain injury (TBI) is a devastating cause of death and disability. Progression of non-fatal cases of
TBI often leaves patients at increased risk for subsequent injury and disease. Improved understanding of the
mechanisms of TBI is fundamental to improving strategies for both prevention and treatment. Recent
experiments show evidence that the brain softens (i.e., its stiffness is reduced) following TBI. Little is known
about the significance or mechanisms of this softening, but it is typically believed to result from edema. Recent
data from our team show that overstretch (deformation beyond typical physiological conditions) changes the
structure and function of cerebral arteries. These changes include softening, with reductions in stiffness as
high as 80% for large, but still sub-rupture, deformations. Given the predictions of finite element (FE) models
that cerebral vessels significantly influence the structural response of the brain, it follows that softened blood
vessels likely contribute to overall brain softening. It is, of course, also possible that brain tissue itself softens
with deformation. Based on these data, our guiding hypothesis is that TBI-induced deformation directly softens
the brain and its associated tissues, leading to reduced constraint of brain motion and thus contributing to
increased risk of injury in subsequent trauma. We further hypothesize that softening is a direct function of
strain and that it correlates with both injury severity and subsequent injury susceptibility. If these hypotheses
are true, softening has significant potential as a quantifiable biomarker of both injury severity and subsequent
susceptibility. This is particularly notable since softening can be quantified non-invasively, and within specific
regions, using magnetic resonance elastography (MRE), with potential to be used in diagnosis, treatment, and
definition of recovery status for individual patients. Such data is also expected to be useful for validation of FE
TBI models. Additionally, given that vessel softening occurs at deformations well below those that result in
hemorrhage, this biomarker could provide novel insight into the mechanics of mild TBI. As a step toward
pursuing these hypotheses, the overall objective of this R03 proposal is to obtain preliminary data
demonstrating softening in a large animal model of inertial TBI. This will be accomplished through two aims.
Aim 1 will characterize TBI in the pig. The pig is commonly utilized as a model of inertial TBI because of its
gyrencephalic brain. We have previously utilized this model to study mild, repeated loading and here propose
to extend our model to investigate single loading events producing mild to moderate injury. We will
characterize the new model by defining the relationship between loading conditions and injury severity,
described through both magnetic resonance imaging and histology. Aim 2 will quantify TBI-induced brain tissue
softening using MRE. In addition to the...

## Key facts

- **NIH application ID:** 10871326
- **Project number:** 1R03NS137098-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** KENNETH L MONSON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,878
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871326

## Citation

> US National Institutes of Health, RePORTER application 10871326, Tissue Softening in Traumatic Brain Injury (1R03NS137098-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10871326. Licensed CC0.

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