The Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms

Abstract

Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism.

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

“…During deployments, there is a high overlap in blast and blunt-force traumatic brain injuries (TBIs) (Chandra and Sundaramurthy, 2015; Manners et al, 2016), obscuring the physiological impact of isolated blast exposure in humans (Mac Donald et al, 2016b; MacDonald et al, 2014). This is concerning, because in animal model blast-induced TBI (biTBI) has different signature features than blunt-force TBI (Courtney and Courtney, 2015). Previously, we have linked chronic neurological symptoms related to a combination of blast and TBIs in military personnel to greater inflammation, suggesting that inflammation may contribute to blast related pathology, yet no acute clinical studies to understand this relationship have been undertaken (Devoto et al, 2016).…”

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

“…Similarly, following a moderate FPI, a mixed model of focal and diffuse injury (Thompson et al , 2005), oligomeric and phosphorylated tau are increased acutely: 4h, 24h and 2 weeks post-injury (Gerson et al , 2016; Hawkins et al , 2013). Mild blast TBI, which encompasses both the blast wave and rotational acceleration-deceleration forces and results in diffuse injury, transient axonal injury, and vascular pathology (Courtney and Courtney, 2015; Kovacs et al , 2014), has also been shown to increase tau acutely following injury. For example, mild blast TBI increases phosphorylated tau in rat hippocampus 6h post-injury (Perez-Polo et al , 2015), and a repetitive blast injury consisting of three closely spaced blasts results in total tau levels being increased 24h post-injury in mouse cerebellum (Arun et al , 2013).…”

Visual system pathology in humans and animal models of blast injury

“…Among these, primary injury is the most difficult to distinguish due to its co‐occurrence with events that cause overt physical damage (Bhattacharjee, ). Although primary injury is now known to cause neurological impairments in the absence of other modes of injury, it remains the least understood type of injury and has motivated studies focusing on the spectrum of injuries that result from exposure to blast (Courtney & Courtney, ; Elder & Cristian, ; Hicks, Fertig, Desrocher, Koroshetz, & Pancrazio, ; Nakagawa et al, ; Svetlov et al, ).…”

“…Acceleration‐deceleration, direct cranial transmission of the blast wave, and thoracic transmission are the main pathological events attributed to blast exposure (Courtney & Courtney, ; Goldstein et al, ; Gullotti et al, ). Although neural damage due to acceleration‐deceleration from blast waves traversing the skull is an accepted contributor of blast injury, thoracic transmission was initially the most widely cited mechanism.…”