Document Type


Date of Award

Summer 2018

Degree Name

Master of Science in Biomedical Engineering - (M.S.)


Biomedical Engineering

First Advisor

N. Chandra

Second Advisor

Venkata R. Kakulavarapu

Third Advisor

Bryan J. Pfister


Blast-induced Traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and training sites with long-term neurological and psychological pathologies. Among many pathological sequela of blast TBI, oxidative stress has been identified as a major factor contributing to the pathophysiology of bTBI. Recent studies have demonstrated activation of oxidative stress pathways following blast injury but their distribution among different brain regions as function of post injury time and Blast over pressure (BOP) have not been explored. The present study examines the protein expression of NADP oxidase (NOX) isoforms 1 & 2, corresponding superoxide production, a downstream event of NOX activation as well as the extent of lipid peroxidation adducts of 4-Hydroxynonenol (4-HNE). Based on these results, in the present study, we asked: 1) whether NOX protein levels change as a function of different overpressures in bTBI? 2) Whether such changes follow a temporal pattern? and 3) what are the consequences of NOX protein changes on the downstream events including superoxide production and lipid peroxidation of proteins. The Brain injury was evaluated at 4, 24 hours and 7 days and at 130, 180 and 240 kPa blast overpressures. Results showed that NOX isoform expression display a bi-phasic response wherein, its expression did not change at 130 kPa, whereas a significant increase was first detected in animals exposed to 180 kPa BOP which displayed a further increase at 240 kPa. Examination of temporal changes in NOX protein levels again displayed a biphasic response with a significant increase at 4h post- injury which peaked at 24 h and completely restored to that of control levels at 7 days post-injury. Blast exposure also resulted in increased superoxide levels in different brain regions as well as changes in lipidid peroxidation product 4hydroxynonenol (4HNE) protein adduct formation. Collectively, our results demonstrate that NOX isoforms are upregulated in different brain regions as a function of different overpressures in bTBI and temporally display a biphasic response. Oxidative stress therefore appears to be a higher risk factor in the pathogenesis of bTBI.