Abstract
Blast-induced traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and in training sites with long-term neurological and psychological pathologies. Previous studies from our laboratory demonstrated activation of oxidative stress pathways after blast injury, but their distribution among different brain regions and their impact on the pathogenesis of bTBI have not been explored. The present study examined the protein expression of two isoforms: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 (NOX1, NOX2), corresponding superoxide production, a downstream event of NOX activation, and the extent of lipid peroxidation adducts of 4-hydroxynonenal (4HNE) to a range of proteins. Brain injury was evaluated 4 h after the shock-wave exposure, and immunofluorescence signal quantification was performed in different brain regions. Expression of NOX isoforms displayed a differential increase in various brain regions: in hippocampus and thalamus, there was the highest increase of NOX1, whereas in the frontal cortex, there was the highest increase of NOX2 expression. Cell-specific analysis of changes in NOX expression with respect to corresponding controls revealed that blast resulted in a higher increase of NOX1 and NOX 2 levels in neurons compared with astrocytes and microglia. Blast exposure also resulted in increased superoxide levels in different brain regions, and such changes were reflected in 4HNE protein adduct formation. Collectively, this study demonstrates that primary blast TBI induces upregulation of NADPH oxidase isoforms in different regions of the brain parenchyma and that neurons appear to be at higher risk for oxidative damage compared with other neural cells.
Highlights
Traumatic brain injury (TBI) resulting from different episodes of head trauma is one of the leading causes of morbidity and death in both military personnel and civilian populations
To assess the diffuse nature of primary blast in the posterior region of the brain, NOX1 and NOX2 protein levels were determined in the cerebellum, and we found that similar to cerebral hemisphere, cerebellar levels of NOX1and NOX2 protein were significantly increased (60% and 40%, respectively, p < 0.05) (Fig. 2)
The rationale in examining these regions is as follows: (a) NOX1 and NADPH oxidase (NOX) 2 isoforms are ubiquitously expressed in all brain regions, (b) the effect of shockwave propagation over the entire brain is not known, and (c) to use NOX1 and NOX2 as markers to evaluate whether there exists any selective vulnerability of various brain structures, a phenomenon that has not been investigated previously
Summary
Traumatic brain injury (TBI) resulting from different episodes of head trauma is one of the leading causes of morbidity and death in both military personnel and civilian populations. TBI causes approximately 1.5 million deaths and hospitalizations annually in the United States.[1,2,3] Blast-induced TBI (bTBI) is the most prevalent form of brain injury in soldiers in combat zones because of the widespread use of high explosives in the war zones, and an increasing number of cases has been reported in civilian populations with the use of improvised explosive devices by insurgents.[4,5]. Among many pathological factors associated with either primary mechanical injury or secondary biochemical cascades, oxidative stress has been shown to play a major role in various models of TBI.[6,7] The main inducers of oxidative stress are reactive oxygen species (ROS), which include superoxide (O2,-), hydroxyl radical (HO,), and hydrogen peroxide (H2O2).[8,9] ROS are normally produced in several metabolic reactions, including redox-reactions (oxidation/reduction), oxidative phosphorylation, and in a normal
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
