Explosions are physical phenomena that result in the sudden ... which extends outward from the explosion in a radial fash- ...... MP-HFM-207, Halifax, Canada.
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Blast Injuries and Blast-Induced Neurotrauma Overview of Pathophysiology and Experimental Knowledge Models and Findings Ibolja Cernak
CONTENTS 45.1 Introduction...................................................................................................................................................................... 631 45.2 Blast-Body and Blast-Brain Interactions.......................................................................................................................... 632 45.3 Modifying Potential of Systemic Changes Caused by Blast............................................................................................ 633 45.3.1 Air Emboli............................................................................................................................................................ 633 45.3.2 Activation of the Autonomous Nervous System................................................................................................... 634 45.3.3 Vascular Mechanisms........................................................................................................................................... 635 45.3.4 Systemic Inflammation......................................................................................................................................... 636 45.4 Requirements for Blast-Induced Injury Models............................................................................................................... 636 45.5 Choice of Models.............................................................................................................................................................. 636 45.5.1 Experimental Environment Generating Blast...................................................................................................... 638 45.6 Blast-Induced Neurotrauma.............................................................................................................................................. 640 45.6.1 Animal Models of BINT...................................................................................................................................... 640 45.7 Conclusion........................................................................................................................................................................ 641 References.................................................................................................................................................................................. 641
45.1 INTRODUCTION Explosions are physical phenomena that result in the sudden release of energy; they may be chemical, nuclear, or mechanical. This process results in a near-instantaneous pressure rise above atmospheric pressure. The positive pressure rise (“overpressure”) compresses the surrounding medium (air or water) and results in the propagation of a blast wave, which extends outward from the explosion in a radial fashion. As the front or leading edge of the blast wave expands, the positive phase is followed by a decrease in pressure and the development of a negative wave (“underpressure”) before subsequently returning to baseline. Figure 45.1 shows an idealized form of a shock wave (Friedländer wave) (Friedlander, 1955) generated by a spherical, uncased explosive in the air in free field conditions. The extent of damage from the blast wave mainly depends on five factors: (1) the peak of the initial positive-pressure wave (an overpressure of 690–1,724 kPa, for example, 100–250 psi, is considered potentially lethal) (Champion et al., 2009); (2) the duration of overpressure; (3) the medium of explosion; (4) the distance from the incident blast wave; and (5) the degree of focusing because
of a confined area or walls. Intensity of an explosion pressure wave declines with the cubed root of the distance from the explosion. Thus, a person 3 m (10 ft) from an explosion experiences nine times more overpressure than a person 6 m (20 ft) away. Additionally, explosions near or within hard solid surfaces can be amplified two to nine times because of shock wave reflection (Rice and Heck, 2000). Indeed, it was observed that victims positioned between a blast and a building often suffer injuries two to three times the degree of the injury of a person in an open space. People exposed to explosion rarely experience the idealized pressure-wave form. Even in open-field conditions, the blast wave reflects from the ground, generating reflective waves that interact with the primary wave, thus changing its characteristics. In a closed environment (such as a building, an urban setting, or a vehicle), the blast wave interacts with the surrounding structures and creates multiple wave reflections, which, interacting with the primary wave and between each other, generate a complex wave (Ben-Dor et al., 2001; Mainiero and Sapko, 1996). Blast injuries are characterized by interwoven mechanisms of systemic, local, and cerebral responses to blast exposure (Cernak, 2010). When a blast generated by explosion strikes
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Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects
PSO
Pressure
Positive impulse, is
PS(t) Ambient
tA + tO
tA
PO
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Negative impulse IS
tA + tO + tO
P SO PS (t)
Positive phase tA t=0
Negative phase
Duration tO
Duration tO
Time after explosion
FIGURE 45.1 The Friedländer wave describing an ideal blast from a spherical source in an open environment. t0 is the time at which the pressure began to rise above ambient pressure. Positive magnitude is the difference between peak pressure and ambient pressure. Positive duration is the time between t0 and when the pressure goes below ambient pressure. Positive impulse is the integral of the pressure-time trace during the positive phase. Negative magnitude is the difference between ambient and peak negative pressure. (From Ngo, T. et al., EJSE Special Issue: Loading on Structures, 76–91, 2007.)
a living body, part of the shock wave is reflected and another fraction is absorbed becoming a tissue-transmitted shock wave. The transferred kinetic energy causes low-frequency stress waves that accelerate a medium from its resting state, leading to rapid physical movement, displacement, deformation, or rupture of the medium (Clemedson, 1956; Clemedson and Criborn, 1955). Thus, a militarily relevant blast injury model should be able to capture and measure these phenomena based on sufficient knowledge of shock wave physics, the characteristics of the injurious environment generated by an explosion, and the clinical manifestations and sequelae of the injuries. The purpose of this chapter is to outline the pathophysiology of blastbody/blast-brain interactions and to summarize the scientific evidence to date for the selection of appropriate experimental models for characterizing and understanding these interactions.
45.2 BLAST-BODY AND BLAST-BRAIN INTERACTIONS Conceptually, explosive blast may have five distinct effects on the body (Figure 45.2): (1) primary blast effects causing injuries as sole consequences of the shock wave–body interaction; (2) secondary blast effects from the fragments of debris propelled by the explosion and connecting with the body, causing penetrating and/or blunt trauma; (3) tertiary blast effects from acceleration/deceleration of the body or part of the body (Richmond et al., 1961); (4) quaternary blast effects caused by the transient but intense heat of the explosion (flash burns) (Mellor, 1988); and (5) quinary blast
effects caused by “post-detonation environmental contaminants,” such as bacteria and radiation from dirty bombs, and tissue reactions to fuel and metal residues, among others (Kluger et al., 2007). Often, especially in the case of moderate-to-severe blast injuries, the multiple blast effects interact with the body simultaneously. In some literature sources, such an injurious environment and related injuries are referred to as “blast plus” scenarios (Moss et al., 2009). When a shock wave generated by detonating a highenergy explosive strikes a living body, several physical events take place: a fraction of the shock wave is reflected, whereas another fraction of the shock wave energy is absorbed and propagates through the body as a tissue-transmitted shock wave (Clemedson and Criborn, 1955). Different organ and body structures differ in their reaction. Nevertheless, tissues typically respond (1) either on the impulse of the shock wave—this response is of longer duration—or (2) on the pressure variations of the shock wave, and this response is in a form of oscillations or pressure deflections of shorter duration (Clemedson and Pettersson, 1956). For example, basic experiments showed that tissues in the abdomen and costal interspaces react with typical impulse response, whereas the rib and the hind leg responded with a more or less pure maximum pressure type curve (Clemedson and Granstom, 1950; Clemedson et al., 1956, 1969). The energy of the primary blast shock wave is either absorbed or transformed into the kinetic energy of a medium, which could be solid, liquid, gas, or plasma, when the interaction between them occurs (Clemedson and Jonsson, 1961). The transferred kinetic energy, then, moves and
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Blast Injuries and Blast-Induced Neurotrauma
Secondary blast-induced neurotrauma (penetrating head injury)
Primary blast-induced neurotrauma (without a direct blow to the head) Kinetic energy transfer to the CNS Lung injury-induced hypoxia/ischemia Hemorrhage-induced hypoxia/ischemia Hormones released from injured tissue
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Tertiary blast mechanisms (i.e., effect of the impacts with other objects)
Site of impact “coup”
Injury to the brain opposite the site of impact “contrecoup”
Secondary blast mechanisms (i.e., effect of the missiles being propelled by blast force)
Primary blast mechanisms (i.e., effects of the blast wave itself )
Tertiary blast-induced neurotrauma (coup-contrecoup)
FIGURE 45.2 Complex injurious environment resulting from blast. Primary blast effects are caused by the blast wave itself (excludes penetrating and blunt force injury); secondary blast effects are caused by particles propelled by the blast (penetrating or blunt force injury); tertiary blast effects are caused by acceleration and deceleration of the body and its impact with other objects (penetrating or blunt force [including “coup-contrecoup”] injury). (From Cernak I. and L.J. Noble-Haeusslein. J Cereb Blood Flow Metab. 30:255–66. 2010. With permission.)
accelerates elements of the medium from their resting state with a speed that depends on the density of the medium; this leads to the medium's rapid physical movement, displacement, deformation, or rupture (Clemedson and Pettersson, 1956). As a result, the main physical mechanisms of the blast-body interaction and subsequent tissue damage include spalling, implosion, and inertia (Benzinger, 1950). Spallation occurs at the boundary between two media of different densities when a compression wave in the denser medium is reflected at the interface. Implosion happens in a liquid medium containing a dissolved gas. Because the shock wave penetrates such a medium, it compresses the gas bubbles, raising the pressure in the bubbles much higher than the initial shock pressure; after the pressure wave passes, the bubbles can rebound explosively and damage surrounding tissue. Inertial effects also occur at the interface of the different densities; the lighter object will be accelerated more than the heavier one, creating a large stress at the boundary (Sanborn et al., 2012) Recent results suggest a frequency dependence of the primary blast effects. High-frequency (0.5–1.5 kHz) lowamplitude stress waves have been observed to target mostly organs that contain abrupt density changes from one medium to another (for example, the air–blood interface in the lungs or the blood–parenchyma interface in the brain). On the other hand, low-frequency (
