Mild Neurotrauma Indicates a Range-Specific Pressure Response to Low Level Shock Wave Exposure

Abstract

Identifying the level of overpressure required to create physiological deficits is vital to advance prevention, diagnostic, and treatment strategies for individuals exposed to blasts. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute neurological alterations occurred. Rats were exposed to a single low intensity shock wave at a pressure of 0, 97, 117, or 153 kPa. Following exposure, rats were assessed for acute cognitive alterations using the Morris water maze and motor dysfunction using the horizontal ladder test. Subsequently, histological analyses of three brain regions (primary motor cortex, the hippocampal dentate gyrus region, and the posteromedial cortical amygdala) were conducted. Histological parameters included measuring the levels of glial fibrillary acidic protein (GFAP) to identify astrocyte activation, cleaved caspase-3 for early apoptosis identification and Fluoro-Jade B (FJB) which labels degenerating neurons within the brain tissue. The results demonstrated that an exposure to a single 117 kPa shock wave revealed a significant change in overall neurological deficits when compared to controls and the other pressures. The animals showed significant alterations in water maze parameters and a histological increase in the number of GFAP, caspase-3, and FJB-positive cells. It is suggested that when exposed to a low level shock wave, there may be a biomechanical response elicited by a specific pressure range which can cause low level neurological deficits within the rat. These data indicate that neurotrauma induced from a shock wave may lead to cognitive deficits in short-term learning and memory of rats. Additional histological evidence supports significant and diffuse glial activation and cellular damage. Further investigation into the biomechanical aspects of shock wave exposure is required to elucidate this pressure range-specific phenomenon.

Blast induced neurotrauma causes overpressure dependent changes to the DNA methylation equilibrium

“…Previous work has shown varying blast magnitudes can lead to different responses at the cellular level [8,12]. Glial cell activation has been shown to be blast dependent where low level blasts lead to neuroprotective efforts and more severe exposures lead to inevitable cell death [8,12]. Changes in DNA methylation have been implicated in neuroinflammation [20,21].…”

“…Differences among the various blast magnitudes tested were evident in both the prefrontal cortex and hippocampus indicating a different cellular response to pressure severity. Previous work has shown varying blast magnitudes can lead to different responses at the cellular level [8,12]. Glial cell activation has been shown to be blast dependent where low level blasts lead to neuroprotective efforts and more severe exposures lead to inevitable cell death [8,12].…”

“…Oxidative stress may be another factor in the dynamic methylation levels following BOP exposure. Oxidative stress is a well-documented consequence of BINT and TBI [8][9][10]13,14,30] and has been shown to effect DNA methylation [31]. Oxidative stress and reactive oxygen species (ROS) accumulation can lead to DNA damage which prevents the methylation of nucleotides [32].…”

“…Clinical symptoms of TBI are influenced largely in part by the underlying cellular and molecular changes that occur subsequent to the mechanical insult. Increased neuronal degeneration and death, neurotransmitter release, axonal damage, inflammation and oxidative stress are characteristic of the injury pathology [8][9][10][11][12][13][14][15]. Aberrant expression patterns have been observed following BINT and correlated with physical outcomes including inflammation and oxidative stress, as well as behavioral outcomes including memory and anxiety [12][13][14][15][16].…”

On the prospective contributions of the shock physics community to outstanding issues concerning blast-induced traumatic brain injury

“…However, it is unfortunately not standard practice. While few researchers have purposely designed experiments to generate scaled-down exposure conditions [14,32,33] against small mammals, others expose animal models to blast parameters relevant to humans [27,[34][35][36][37][38][39][40][41][42][43]. Assuming mass scaling is relevant to bTBI, some of these exposures may effectively result in exposing an animal model to nuclear-sized blasts [29].…”