Explosive Blast-Induced Brain Injury Studies

Three hundred thousand. According to a recent Rand Corporation study, of the 1,640,000 U.S. troops deployed abroad on support missions in Iraq and Afghanistan, 300,000 have reported symptoms of traumatic brain injury (TBI). Nearly one out of every five (19.5%) of deployed soldiers returning home can expect to have experienced traumatic brain damage. When including soldiers exhibiting signs and symptoms of posttraumatic stress disorder (PTSD), nearly a third, 31%, of U.S. troops coming home today suffer from some form of serious brain injury.

Yet, for all the damage these invisible injuries inflict, strikingly little is known about them. While PTSD is psychological by nature, rooted in the psychological repercussions of experiencing extreme stress, traumatic brain injury is itself inherently physical, caused by a mechanical insult to the brain. Today, through a collaborative effort with other laboratories throughout the United States, Yale Professor of Psychology Nihal de Lanerolle is attempting to shine light on this silent killer by investigating the neuropathological underpinnings of a growing yet understudied type of brain injury: mild traumatic brain injury caused by an explosive blast.

Explosive-induced TBI

In the most general sense, traumatic brain injuries come in two varieties: open and closed head injuries. Open, or penetrating, injuries, are usually caused by a projectile puncturing the skull and breaching the dura mater, thus exposing brain tissue to the outside environment. This type of wound – including gunshot wounds, severe skull fractures, and, notably, the case of Phineas Gage, one of the earliest documented cases of severe brain trauma – results in obvious, macroscopic physical damage.

In contrast, closed injuries are rarely as gruesome as their open counterparts, even though they can be just as damaging. Because these injuries neither puncture the dura mater nor necessarily breach the skull or scalp, they tend to be very hard to detect in the field. In fact, most diagnostic tools used to detect closed TBI are either inductive, including analyzing the mechanism of injury, or behavioral, such as examining the patient. Even in a hospital, this type of injury is frustratingly difficult to detect, as conventional imaging techniques like magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and computed tomography (CT) scans can only detect gross internal deformities. Unfortunately, this elusiveness leads many patients suffering from this type of injury to be either undertreated or altogether ignored.

Traumatic brain injuries are further classified according to their severity, from mild to moderate to severe. While exact classifications vary by source and purpose, the Department of Veteran Affairs (VA) and Department of Defense (DoD) have accepted a common empirically-derived classification for TBI, as seen in Table 1. According to these guidelines, mild TBI is characterized by normal structural imaging, a loss of consciousness (LOC) for up to half an hour, an altered level of consciousness (ALOC) for up to a day, and post-traumatic amnesia (PTA) for up to a day, as well as a Glasgow Coma Scale (GCS) score of between 13-15 (Table 2). The moderate and severe classifications incrementally increase the severity of each category, but the same guidelines apply to classify each type of injury.

Table 1: TBI Classifications used by the Veterans’ Health Administration and Department of Defense.
Table 2: The Glasgow Coma Scale (GCS), one of the most common and reliable neurological scales to assess cognitive function and competency.

De Lanerolle, together with Yale colleague Dr. Jung Kim, has chosen to focus on investigating the underlying neuropathology of a certain type of mild TBI: explosive blast-induced mild TBI. Just as there are many ways to break a bone, there are many ways to get a TBI, all of which lead to different injury patterns. For instance, TBIs caused by car crashes commonly cause patterns of injury known as coup contrecoup injuries. These injuries, resulting from the brain colliding with the front of the skull, ricocheting back, and then colliding with the back of the skull, cause anterior and posterior bruising to the brain. In contrast, TBI associated with falling down has been linked with diffuse damage to the cerebellum and other brain regions. Similarly, it was expected that mild TBI resulting from proximity to explosions would exhibit a distinct pattern of injury. From the detonation point of an explosive device, a wave of high pressure travels at sonic speeds straight through the skull and brain of any person within its field. Whether such a pressure blast passing through the human brain and the skull would actually cause any physical damage to the brain itself was unknown.

A diagram of the physical mechanism that causes coup contrecoup injuries.

Analog Studies

To investigate the underlying neuropathological consequences of explosive induced TBI, de Lanerolle subjected 31 anesthetized human analogs to mild blast conditions in three operationally relevant scenarios.

In the first scenario, a free field simulation, the analogs were exposed to a measured level of explosive blast within a tube with a diameter of 10 feet. The large diameter was selected to minimize wave interference from the blast, thereby best simulating the longitudinal waves experienced from a blast in an open environment such as a park or square. In the second scenario, a “tactical vehicle surrogate,” essentially a model of a Humvee, was used to simulate the significantly more complex wave propagations caused by interference within an enclosed space. In the third and final scenario, a four-walled structure was used to similarly model the complex wave propagations experienced when a blast occurs within a building. Two weeks after being exposed to these blasts, the analog’s brains were prepped for analysis and stained for neuropathological examination.

Figure 1. Axons around the ventricles of the brain (periventricular) are damaged in TBI. The damaged axons accumulate a protein called beta amyloid precursor protein.

While de Lanerolle and his colleagues expected to discover generalized neuronal loss with diffuse axonal injury (DAI) as in TBI from other types of trauma, their analysis revealed a strikingly different pattern of injury. They observed axonal injury centered on the periventricular regions of the brain (Figure 1). While peculiar at first, this unique distribution is highly consistent with the mechanism of injury: an explosive blast. As with all explosive blast injuries, the damage tends to be most severe between surfaces of different densities, as pressure waves expand different densities to different degrees. In other words, the less dense region expands more than the denser region. In the case of the analog brains, the less dense ventricles appear to have expanded significantly more than the surrounding brain tissue, causing the shearing and tearing of axons.

Additionally, they observed the activation and proliferation of two other types of non-neuronal cells in the brain: astrocytes and microglia. The astrocyte numbers were particularly elevated in the hippocampus of the brain, a structure important for memory function. Microglial activation was abundant in the corpus callosum, a major fiber tract that transfers information between the two hemispheres of the brain (Figure 2). In addition to various other functions, these two cell types are known to contribute to the process of neural inflammation. Thus, their activation so soon after exposure to a blast pressure wave clearly suggests the early initiation of physical injury to certain critical brain areas.

Figure 2. Microglial activation in deep white matter areas. Side A is the control group, while Side B is the blast-exposed analogs.

Human Studies and Future Direction

With the neuropathological basis for these injuries roughly established, de Lanerolle, together with Yale colleague Dr. Hoby Hetherington, has transitioned to studying the effects of blast injuries on retired Special Forces soldiers who were exposed to multiple explosive blasts in the line of duty. Their conditions present a wide variety of neurological symptoms, including significant loss of memory function, and are being studied to further shed light on explosive blast induced TBI. Utilizing magnetic resonance spectroscopic imaging (MRSI) with special imaging coils developed by Hetherington, they are examining spatial differences in the concentration of creatine, choline, and N-acetylaspartic acid (NAA), several important molecules associated with proper neural metabolism. This work has already for the first time indicated a physical underpinning for their symptoms: bilateral neuronal injury and axonal demyelination of the hippocampi. Moreover, these results are consistent with the patterns observed from de Lanerolle’s previous human analogue studies.

While this field is still in its infancy, the potential for future advancement is vast. Ranging from the widespread implementation of “docimeters” into the helmets of soldier to monitor each soldier’s blast pressure exposure, to the development of brain imaging tools that could detect pathological changes that reliably correlate with neurological changes, to the development of neuroprotective drugs, the potential to assuage the invisible burdens hefted upon those who risk life and limb every day is as inspirational as it is humbling.

About the Author
JOHN URWIN is a sophomore prospective Biology major in Jonathan Edwards College. He is a contributing writer for the Yale Scientific Magazine and works in Professor Colón-Ramos’ lab researching nervous system development in C. elegans.

The author would like to greatly thank Professor Nihal de Lanerolle for his time, assistance, and continued devotion to his research.

Further Reading
Tanielian, Terri, and Jaycox, Lisa H. Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. (Rand Corporation, 2008).
De Lanerolle, Nihal. “Characteristics of an Explosive Blast-Induced Brain Injury in an Experimental Model.” (American Association of Neuropathologists, 2011).
Ashley, Mark J. Traumatic Brain Injury: Rehabilitation, Treatment, and Case Management, 3rd edition. (CRC Press, 2010).