Biological cavitation and protein profiles as unique hallmarks of blast-induced traumatic brain injury
Date
2023-08
Authors
Marsh, Jenny L.
Major Professor
Advisor
Bentil, Sarah A
Sakaguchi, Donald S
Stegemoller, Elizabeth
Hsu, Ming-Chen
Passalacqua, Alberto
Committee Member
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Abstract
The mechanisms which connect head trauma to the signs and symptoms associated with
traumatic brain injury (TBI) remain unclear. There is a particularly limited understanding of
how exposure to a blast leads to cellular changes and cognitive symptoms. To better understand
these blast-induced traumatic brain injuries (bTBIs) it is essential to utilize improved
experimental and computational models to identify specific characteristics of blast compared with
other modes of injury.
This dissertation focuses on two potential distinguishing features of bTBI. First, cavitation is
explored as a mechanism of bTBI using a novel three-dimensional shock tube model. The shock
tube experiments demonstrated the ability to record cavitation behavior through high speed
images, as well as pressure recordings, using blast overpressures which could yield mild bTBI.
This model was applied to cavitation as a brain injury mechanism by quantifying the effects of
several biological and blast parameters that mimic the real conditions which lead to injury. These
findings were then used to validate machine learning algorithms for the prediction of cavitation
behavior, based on fluid properties. This experimental model can be used in future work to
quantify the impacts of other biological parameters on cavitation behavior, which will facilitate a
more comprehensive assessment of the role of cavitation in bTBI than has been previously
possible. The machine learning algorithms can also be expanded to assess the relationship
between cavitation and brain injury severity, which will provide further evidence on the role of
cavitation, and potentially improve diagnostic capabilities.
The second portion of the dissertation focuses on protein biomarker expression in bTBI.
Biomarkers receive increasing attention in TBI research recently, for their prognostic and
diagnostic capability. However, there is little work which differentiates protein expression by
mode of injury. Identifying divergent protein changes (if they exist) would be a key development
in understanding unique pathophysiology associated with different modes of injury. Since swine
models are increasingly utilized in bTBI models, but have not been frequently used in biomarker
studies, the concentration of a common TBI biomarker, Glial Fibrillary Acidic Protein (GFAP)
was evaluated in abattoir swine. The values found in this study are the first attempt to establish
normal reference levels, and quantify the inter-subject variability between subject animals. These
results will facilitate continued development of swine-biomarker models for bTBI.
Taken together, the results of the present work provide significant additions to experimental
and computational models for distinguishing features of blast-induced traumatic brain injury
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dissertation