Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model

•Blast exposures are associated with traumatic brain injury (TBI); during recent conflicts most of these have been classified as mild TBI (mTBI).•The role and mechanisms of primary blast wave injury remain controversial. We review blast models of TBI including shock tubes and open-field blast.•Our analyses of behavioral and pathological findings show that low level blast exposures (peak pressure200kPa).•We present preliminary findings obtained from a reproducible open-field blast murine model of mTBI representing a primary low level blast injury. Within scalability limits, this model closely mimics low level battlefield blast exposures and offers opportunities to advance the understanding of blast physics, resulting neuropathology, and underlying mechanisms leading to chronic effects of mTBI. Blast exposures are associated with traumatic brain injury (TBI) and blast-induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called “the invisible injury” of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI.