title: Blast induces oxidative stress, inflammation, neuronal loss and subsequent short-term memory impairment in rats.
abstract: Molecular and cellular mechanisms of brain injury after exposure to blast overpressure (BOP) are not clearly known. The present study hypothesizes that pro-oxidative and pro-inflammatory pathways in the brain may be responsible for neuronal loss and behavioral deficits following BOP exposure. Male Sprague-Dawley rats were anesthetized and exposed to calibrated BOP of 129.23±3.01kPa while controls received only anesthesia. In situ dihydroethidium fluorescence staining revealed that BOP significantly increased the production of reactive oxygen species in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assay demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-γ and monocyte chemoattractant protein-1, in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition paradigm showed a significant impairment in the short-term memory at 2weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in BOP-induced neuronal loss and behavioral deficits. It may provide a foundation for defining a molecular and cellular basis of the pathophysiology of blast-induced neurotrauma (BINT). It will also contribute to the development of new therapeutic approaches selectively targeting these pathways, which have great potential in the diagnosis and therapy of BINT.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Electronic address: hjcho79@vt.edu.
authors.forename: H J
authors.initials: HJ
authors.lastname: Cho
authors.forename: V S S S
authors.initials: VS
authors.lastname: Sajja
authors.forename: P J
authors.initials: PJ
authors.lastname: Vandevord
authors.forename: Y W
authors.initials: YW
authors.lastname: Lee
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001753:Blast Injuries / Q000150:complications* / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C100745:Aif1 protein, rat; D029681:Arabidopsis Proteins; D002135:Calcium-Binding Proteins; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008840:Microfilament Proteins; D007371:Interferon-gamma; D010751:Phosphopyruvate Hydratase; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis
keywords: BINT; BOP; BSA; C(T); DHE; ELISA; GAPDH; IFN-γ; IL-6; MCP-1; NADPH; NOR; NeuN; OEF; OIF; Operation Enduring Freedom; Operation Iraqi Freedom; PBS; ROS; RT-PCR; T1; T2; TBI; TNF-α; blast overpressure; blast-induced neurotrauma; bovine serum albumin; dihydroethidium; enzyme-linked immunosorbent assay; glyceraldehyde-3-phosphate dehydrogenase; inflammation; interferon-γ; interleukin-6; monocyte chemoattractant protein-1; neuronal loss; neuronal nuclei; nicotinamide adenine dinucleotide phosphate; novel object recognition; oxidative stress; phosphate-buffered saline; reactive oxygen species; reverse transcriptase-polymer chain reaction; short-term memory impairment; threshold cycle; traumatic brain injury; trial 1; trial 2; tumor necrosis factor-α