Citation

Vogel Iii EW, Rwema SH, Meaney D, Bass C', Morrison Iii B. J. Neurotrauma 2016; 34(5): 1063-1073.

Affiliation

Columbia University, Biomedical Engineering , 1210 Amsterdam Ave. , MC8904 , New York, New York, United States , 10027 ; bm2119@columbia.edu.

Copyright

(Copyright © 2016, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4578

PMID

27573357

Abstract

Blast-induced traumatic brain injury (bTBI) is a major threat to U.S. service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked, neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal functional.

Language: en