Mechanisms of Primary Blast-Induced Traumatic Brain Injury: Insights from Shock-Wave Research

Abstract

Traumatic brain injury caused by explosive or blast events is traditionally divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury phase represents the response of brain tissue to the initial blast wave. Among the four phases of bTBI, there is a remarkable paucity of information about the cause of primary bTBI. On the other hand, 30 years of research on the medical application of shockwaves (SW) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by supersonic flow. The resultant tissue injury includes several features observed in bTBI, such as hemorrhage, edema, pseudoaneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation, are all important factors in determining the extent of SW-induced tissue and cellular injury. Herein we describe the requirements for the adequate experimental set-up when investigating blast-induced tissue and cellular injury; review SW physics, research, and the importance of engineering validation (visualization/pressure measurement/numerical simulation); and, based upon our findings of SW-induced injury, discuss the potential underlying mechanisms of primary bTBI.

Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: Role of compromised cell membrane integrity

“…Collectively, these data suggest that blast exposure affects the cell membrane integrity of brain and peripheral organs which can lead to widespread bidirectional passage of molecules. The various potential mechanisms of cell membrane disruption after blast exposure have been described in detail by Nakagawa et al [18].…”

Oxy-acetylene driven laboratory scale shock tubes for studying blast wave effects

“…12 Most current shock tube designs do not meet all of the requirements for fidelity of the pressure wave and accessibility in terms of facilities and cost. 13 The utility of a modular shock tube design has been demonstrated in both compression-driven and blast-driven designs. For example, in the 1950s Henshall 8 built a modular, compressiondriven shock tube that consisted of mahogany wood channels with a square cross section.…”

Numerical investigation of the effects of shock tube geometry on the propagation of an ideal blast wave profile

“…Exposure to incident BOP waves is known to damage the hollow gas-filled organs such as ears, lungs, and intestines [1][2][3][4]. Traumatic brain injury and blast-induced neurotrauma upon exposure to blast waves have also been confirmed in animal studies [5][6][7][8][9]. In order to reproduce the ideal blast wave profiles, the proper designs of these studies are appropriate to replicate field conditions in the laboratory.…”

“…P * is the peak pressure, P 0 is the ambient pressure, and t d is the positive phase duration can produce more realistic pressure-time profiles than the compression-driven ones, but their operation requires reliable facilities and is more dangerous due to the use of high explosive materials. Most current shock tube designs do not meet all requirements for fidelity of the pressure wave and accessibility in terms of facilities and cost [9]. The blast wave profile not only determines the survival of animal models, but also the acute biomechanical injuries and the chronic biochemical sequelae [16].…”