Quantitative proteomic profiling in brain subregions of mice exposed to open-field low-intensity blast reveals position-dependent blast effects

Abstract

The neurological consequences of combat blast-induced neurotrauma (BINT) pose important clinical concerns for military service members and veterans. Previous studies have shown that low-intensity blast (LIB) results in BINT with multifaceted characteristics in mice exposed to open-field blast in prone position. Although the prone position is natural for rodents, experimental models of blast using this position do not represent common scenarios of human standing while being exposed to blast during deployment or military training. In this study, we used our previously developed BINT mouse model of open-field LIB with mice in an upright position and then used quantitative proteomics and multiple bioinformatic approaches to analyze brain tissue taken from multiple subregions during the acute post-injury phase. We identified: (1) region-specific BINT-induced proteome changes, which were significantly and differently influenced by animal positioning (upright vs. prone): the upright positioning caused more significant protein alterations in cortex and cerebellum, which were less significant in striatum as compared to prone position; (2) synapse- and mitochondrion-related damage contributed to BINT in both positions; and (3) some molecular signatures were exclusively and/or oppositely regulated in two positions. This study delineates the molecular signatures of the position-dependent blast effects, indicating the importance of brain–body position for BINT translational studies and for modeling the location and extent of position-related blast injuries.