Citation

Sajja VS, Galloway M, Ghoddoussi F, Kepsel A, Vandevord P. J. Neurosci. Res. 2013; 91(4): 593-601.

Affiliation

School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, Virginia.

Copyright

(Copyright © 2013, John Wiley and Sons)

DOI

10.1002/jnr.23179

PMID

23335267

Abstract

Blast-induced neurotrauma (BINT) leads to deterioration at the cellular level, with adverse cognitive and behavioral outcomes. The nucleus accumbens (NAC) plays an important role in reward, addiction, aggression, and fear pathways. To identify the molecular changes and pathways affected at an acute stage in the NAC, this study focused on a time course analysis to determine the effects of blast on neurochemical and apoptotic pathways. By using a rodent model of BINT, acute damage to the NAC was assessed by proton magnetic resonance spectroscopy ((1) H-MRS), high-performance liquid chromatography, immunohistochemistry, and Western blotting. The results demonstrated ongoing neuroprotective effects from elevated levels of Bcl-2, an antiapoptotic marker, at 24 hr and N-acetyl aspartate glutamate at 48 hr following blast exposure. Selective loss of serotonin levels at 24 hr, increased levels of inflammation (elevated glycerophosphocholine at 48 and 72 hr), and increased levels of glial fibrillary acidic protein were also observed at 24 and 48 hr, leading to disruptive energy status. Furthermore, active cell death was indicated by the increased levels of the apoptotic marker Bax, decreased actin levels, and signs excitotoxicity (glutamate/creatine). In addition, increased evels of caspase-3, an apoptotic marker, confirm active cell death in NAC. It is hypothesized that blast overpressure causes inflammation and neurochemical changes that trigger apoptosis in NAC. This cascade of events may lead to stress-related behavioral outcomes and psychiatric sequelae. © 2013 Wiley Periodicals, Inc.

Language: en