A Two-Model Approach to Investigate the Mechanisms Underlying Blast-Induced Traumatic Brain Injury

Blast-induced traumatic brain injury (TBI) is a signature, invisible wound of wars, sustained with long-lasting neuropsychiatric and neurological symptoms. The mechanism of blast-induced TBI has been controversial for a long time. Direct cranial transmission of blast waves was considered by most investigators as the mechanical mechanism by which the blast wave causes mild TBI. Only few investigators hypothesized that thoraco-abdominal vascular/hydrodynamic transmission of blast waves could be the major cause of blast-induced TBI. To separate direct cranial transmission of blast waves from thoraco-abdominal vascular/hydrodynamic mechanism to blast-induced TBI, two “iron lung”-like protective devices are designed for protection of desired parts of the animal body against blast waves. One “Iron lung”-like protective device allows only the animal head to expose to blast waves, and another makes the animal thorax and abdomen only expose to blast waves. The use of the “iron lung”-like protective devices in blast injury research will lead to new insight into the mechanisms underlying blast-induced TBI. Shock tubes have been employed to investigate blast injuries in animals since 1940s. However, many uncertainties are associated with the results obtained from the animal models using shock tubes because a series of complex shock waves generated by shock tubes affect experimental observations and lead to false-positive results in the studies of blast TBI mechanism. A C4 blast generator that generates blast waves by detonation of C4 charge in a free field can be used as a new experimental tool for blast-induced TBI research. A comparative study between two animal models that use traditional shock tube and novel C4 blast generator respectively to induce TBI, will help develop a reliable and valid experimental approach to identify the mechanism of blast-induced TBI. The physical parameters of blast shock waves and the extent and severity of TBI, which are closely associated with the effects of blast shock waves on the brain, need to be analyzed, assessed and compared comprehensively between the two animal models. The two-model comparative approach will contribute to eliminate knowledge gaps regarding blast-induced TBI and to prioritize future TBI research.Blast-induced TBI is the signature injury of the wars in Iraq and Afghanistan and has accounted for significant substantial morbidity and disability among U.S. military members (Martin et al., 2008; Warden, 2006). It has become a major public health problem that results in the loss of many years of productive life and incurs large health care costs (Martin et al., 2008). From 2002 through 2010, the U.S. government has spent about $1.5 billion in blast TBI research and about $6 billion on health care expenditures for more than 280,000 veterans with TBI and posttraumatic stress disorder (Congressional Budget Office, 2012). Blast-induced TBI presents a daunting challenge for the military medical community.The mechanism of blast-induced TBI has been controversial for a long time. However, no satisfying data and results exist to clearly confirm the mechanism of blast TBI. Direct head exposure to blast, skull flexure, and head acceleration were considered by most investigators as the mechanical mechanism by which the blast wave causes mild TBI. Only a few investigators have hypothesized that direct torso impact of blast pressure waves causes noncontact TBI. More recent studies (Assari et al., 2013; Chen et al., 2012; Hue et al., 2013; Sosa et al., 2013; Yeoh et al., 2013) have supported the theory that the major mechanism of blast TBI involves damage to the blood–brain barrier (BBB) and tiny cerebral blood vessels, which is caused by blood surging quickly through large blood vessels from the torso to the brain (Chen and Huang, 2011). Large-scale BBB damage and cerebrovascular insults may be the most important cause of blast-induced TBI after exposure to blast waves.Because the true mechanism of blast-induced TBI is currently unknown, personal blast protection against TBI is still the most difficult challenge facing medical researchers and body armor engineers. Currently, fielded body armor is unable to properly protect the human body against the impact of blast shock wave. In contrast, it could increase the impact force to the body along with blast shock waves, causing more serious “behind armor blunt trauma” (Chen et al., 2012). Clearly, what is required to prevent and mitigate blast-induced TBI is to employ innovative experimental approaches to investigate the mechanisms of blast-induced TBI. The development of the adequate experimental models with defined blast-wave signatures will help elucidate biomechanisms, pathophysiology, histopathology, and neurological and neuropsychological consequences of blast-induced TBI, thus accelerating the discovery of new protective and therapeutic approaches that can effectively reduce the disabilities and serious complications of TBI.