Blast-induced Neurotrauma

Severe TBI has represented the most significant life-threatening trauma to Service Members in Iraq and Afghanistan, but the vast majority of traumatic brain injuries suffered by service members since 2000 have been mTBI, consisting of closed-head injuries without penetration of the skull. More than three-quarters of the TBI suffered in this time period have been caused by blasts.

A critical difference between explosive blast injuries and other brain trauma, Bliese pointed out, is that a blast consists of several potentially injurious events; in air, the most distinctive feature of a blast is the supersonic shock front, through which there is a nearly instantaneous “step” increase in pressure.  Extreme stresses can be induced by shockwave exposure and the process of the loading by shockwave reflection and diffraction around the skull, and consequently how, where, and what stresses are imparted within the brain, remain critical unresolved phenomena. It is largely unknown whether or how these events (e.g., skull deformation, compression and shearing waves, cavitation, and impact acceleration) interact to damage the brain or impair its function and whether or how the incidence of multiple blasts or concussive events can interact to worsen subsequent injuries. Another complicating factor is that blast is a whole-body insult resulting in polytrauma, and the injuries to other parts of the body can greatly influence the evolution and extent of blast injuries to the brain.

“There’s so much we don’t know yet about either the biomechanics or the neurobiology of blast TBI,” said Bliese. “To further complicate matters, most concussions actually don’t happen on the battlefield. They occur because of things like airborne training, combatives [hand-to-hand combat training], or just playing sports. And as we’re discovering with athletes, prior concussions can adversely affect the severity of a subsequent concussion.”

“There’s so much we don’t know yet about either the biomechanics or the neurobiology of blast TBI,” said Bliese. “To further complicate matters, most concussions actually don’t happen on the battlefield. They occur because of things like airborne training, combatives [hand-to-hand combat training], or just playing sports. And as we’re discovering with athletes, prior concussions can adversely affect the severity of a subsequent concussion. Many of our soldiers can literally be playing touch football or basketball in their downtime, take a concussion, and then go out and encounter a blast the next day, followed by another mechanical injury immediately after. We don’t understand the interplay among these combinations: If you had a concussion from one form of injury and then you had a subsequent blast exposure, we don’t really understand the time interval needed to recover, and the factors that determine that heightened vulnerability. We also don’t really understand the mechanism of injury. Is age an associated factor? If you’re a 45-year-old sergeant first class versus an 18-year-old private, and you encounter the same blast, do you feel better or worse? We actually don’t know the answer to that. These are the kinds of issues this group is looking at.”

The center’s Blast-Induced Neurotrauma Branch, led by Dr. Joseph Long and charged with unraveling the complexities of blast injuries – and ultimately with discovering and advancing therapies or policy changes that will help to improve survival and functional outcomes following blast injuries – is facing an additional glaring obstacle: Because of the unique physics of the insult and the currently limited understanding of the parameters underlying blast TBI, the only way to study how and whether a brain has been hurt by blast is to expose it to blast. Consequently, center researchers have pioneered the development of a compressed gas-driven shock tube, in which, in a controlled manner, high pressure gas is used to generate and drive a shock wave to produce a scaleable simulation of the types of blast waves likely to be confronted by troops.

While the work is still fairly young, this research group has achieved interesting and promising results in the past several years, demonstrating that:

• blast exposure, either from explosions or shock tube simulations, can cause axonal injury;

• blast exposure causes changes in brain cells’ energy metabolism and DNA fragmentation, along with neurobehavioral disruptions that to a large extent parallel those described in injured warfighters;

• whole-body blast exposure is followed by the rapid release of tissue enzymes, the levels of which may someday be used to determine a blast’s severity;

• repeated blast exposure causes macrophage activation and the sustained increased circulation of inflammatory mediators, which along with the acute activation of platelets and leukocytes, can worsen the effects of brain injury – suggesting future inflammation-targeted therapies that may help to mitigate acute blast-induced neurotrauma;

• blast-induced brain injuries are appreciably exacerbated by preceding  blast exposure; and

• in addition to protecting lungs and enhancing survival, the use of a thoracic Kevlar® vest provides protection to the brain from the overpressure experienced in whole-body blast exposures.

To build on these productive studies to date, the Blast-Induced Neurotrauma Branch has identified several immediate goals and areas of focus for future work.  In particular, since human brain injury from blast is likely governed by the particular scale, anatomy, and physiology of the human, it is critical to devise means to translate or scale blast induced stress conditions and outcomes from a test species, such as the rat, to human injuries. While establishing these biomechanical and anatomical parameters, branch investigators are also collaboratively evaluating and comparing preclinical animal neuropathological outcomes with human injuries using high-resolution magnetic resonance imaging (MRI), from which notable parallels have become apparent.

Ongoing exploration of the neurobiological underpinnings of blast TBI is driven by the goal of identifying pharmacotherapeutic targets to improve outcome, or recognizing countermeasures to the many factors, such as stressors or nutritional deficiencies, that may increase blast TBI vulnerability.

Ongoing exploration of the neurobiological underpinnings of blast TBI is driven by the goal of identifying pharmacotherapeutic targets to improve outcome, or recognizing countermeasures to the many factors, such as stressors or nutritional deficiencies, that may increase blast TBI vulnerability. Since blast is the leading cause of auditory and visual impairments among warfighters, blast studies include assessments of these neurosensory functions and injuries to underlying structures.  Finally, since neuropathological features of CTE have been recently identified in blast-exposed military veterans, attempts are under way to discern whether multiple blast exposures yield similar brain changes (e.g., tau protein hyperphosphorylation and myelinated axonopathy) in rats, which, with a much shorter life-span than humans or larger species, may be well suited for studies of this chronic nature.