Citation

Cho HJ, Sajja VS, Vandevord PJ, Lee YW. Neuroscience 2013; 253: 9-20.

Affiliation

School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Electronic address: hjcho79@vt.edu.

Copyright

(Copyright © 2013, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.neuroscience.2013.08.037

PMID

23999126

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 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 ± 3.01 kPa while controls received only anesthesia. In situ dihydroethidium (DHE) fluorescence staining revealed that BOP significantly increased production of reactive oxygen species (ROS) in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-γ (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1), in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei (NeuN) in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition (NOR) paradigm showed a significant impairment in the short-term memory at 2 weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in 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 diagnosis and therapy for BINT.

Language: en