High-Fidelity Simulation of Primary Blast: Direct Effects on the Head

Abstract

The role of primary blast in blast-induced traumatic brain injury (bTBI) is controversial in part due to the technical difficulties of generating free-field blast conditions in the laboratory. The use of traditional shock tubes often results in artifacts, particularly of dynamic pressure, whereas the forces affecting the head are dependent on where the animal is placed relative to the tube, whether the exposure is whole-body or head-only, and on how the head is actually exposed to the insult (restrained or not). An advanced blast simulator (ABS) has been developed that enables high-fidelity simulation of free-field blastwaves, including sharply defined static and dynamic overpressure rise times, underpressures, and secondary shockwaves. Rats were exposed in head-only fashion to single-pulse blastwaves of 15 to 30 psi static overpressure. Head restraints were configured so as to eliminate concussive and minimize whiplash forces exerted on the head, as shown by kinematic analysis. No overt signs of trauma were present in the animals post-exposure. However, significant changes in brain 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) and neurofilament heavy chain levels were evident by 7 days. In contrast to most studies of primary blast-induced TBI (PbTBI), no elevation of glial fibrillary acidic protein (GFAP) levels was noted when head movement was minimized. The ABS described in this article enables the generation of shockwaves highly representative of free-field blast. The use of this technology, in concert with head-only exposure, minimized head movement, and the kinematic analysis of the forces exerted on the head provide convincing evidence that primary blast directly causes changes in brain function and that GFAP may not be an appropriate biomarker of PbTBI.

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

“…In addition, an increase in the use of advanced blast simulators (ABS), a shock tube with expanding cross section assembled with an end-wave eliminator, has been observed [43,[47][48][49][50]. ABS are reported to be capable of simulating free-field blast conditions with no loading artefacts.…”

Identification of chronic brain protein changes and protein targets of serum auto-antibodies after blast-mediated traumatic brain injury

“…These mechanisms include immediate [11,12,13] and delayed [14,15] neuronal changes. In many models, classic markers of apoptotic cell death are not present [16]. Cellular mechanisms that are believed to lead to neuronal death and dysfunction after mild TBI or repetitive TBI include diffuse axonal injury and myelin damage, excitotoxicity, dysregulation of the neurovascular unit, inflammation, and oxidative stress [17,18,19,20,21].…”

Hair follicle miRNAs: a novel biomarker for primary blast Induced-Mild traumatic brain injury

“…Additionally, these types of head injuries are less likely to occur at a "far-field" distance. However, the head exposure to the pressure wave generated during explosion can still lead to brain injuries, which are largely composed of cellular/subcellular damages (Jordan, 2013;Sawyer et al, 2016). In such cases, the TBI derived from primary blast is closely associated to mild TBI (mTBI).…”

“…Using an Advanced Blast Simulator (ABS) system, we were able to induce primary blastinduced mTBI in a rat model by head-only exposure to single-pulse shockwaves at a range of pressure intensities (Zhang et al, 2014(Zhang et al, , 2018Sawyer et al, 2016). Four blast intensities ranging from 15 to 30 psi were used to represent the shockwave exposure observed during a low-level far-field explosion event (Sawyer et al, 2016).…”

“…Using an Advanced Blast Simulator (ABS) system, we were able to induce primary blastinduced mTBI in a rat model by head-only exposure to single-pulse shockwaves at a range of pressure intensities (Zhang et al, 2014(Zhang et al, , 2018Sawyer et al, 2016). Four blast intensities ranging from 15 to 30 psi were used to represent the shockwave exposure observed during a low-level far-field explosion event (Sawyer et al, 2016). Based on the publically available microarray gene expression profiles (NCBI Gene Expression Omnibus (GEO) database Accession ID: GSE80371) established from our previous study (Zhang et al, 2018), we utilized gene set analysis approaches such as Sub-network enrichment analysis (SNEA) and Gene set enrichment analysis (GSEA) to assess and functionally characterize the aforementioned miRNAs of interest.…”