Date of Award

Summer 2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Chandra, N.

Second Advisor

Pfister, Bryan J.

Third Advisor

Haorah, James

Fourth Advisor

Kakulavarapu, Venkata R.

Fifth Advisor

Santhakumar, Vijayalakshmi

Sixth Advisor

Rameshwar, Pranela

Abstract

Exposure to shock waves is the leading cause of traumatic brain injury (TBI) in military personnel and blast-induced TBI (bTBI) is considered the signature wound in recent conflicts in Iraq and Afghanistan. Many researchers attempt to replicate field-relevant shock waves in laboratory settings through the use of gas-driven shock tubes in order to investigate the generation and propagation of shock waves and also explore possible mechanisms of bTBI. Among several injury mechanisms of bTBI, damage to the blood-brain barrier (BBB) has been identified as a potential candidate and has been the focus of several clinical and experimental investigations aimed to establish injury baselines and discover timelines for therapeutic intervention for neurotrauma. It is hypothesized that BBB permeability in blast increases with increasing overpressure and varies differentially in different brain regions as a function of time post-injury. In order to test this hypothesis, the blast injury model is characterized and effects of an end reflector plate studied, prior to using this injury model in the study of BBB permeability post-blast injury. BBB breakdown is studied across the frontal cortex, striatum, somatosensory barrel field cortex, thalamus, hippocampus, and cerebellum at fifteen minutes, four, and twenty-four hours at blast overpressures of 35, 70, 130, and 180kPa. Finally, effects of oxidative stress on BBB permeability are delineated at four hours for 180kPa blast exposure, as well as the introduction of a potential treatment for nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated BBB damage following blast injury.

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