A novel mouse model of mild traumatic brain injury using laser-induced shock waves

Abstract

Blast-induced mild traumatic brain injury (mild bTBI) has been a frequent battlefield injury in soldiers during the conflicts in Iraq and Afghanistan. Understanding the pathophysiology and determining effective treatments for mild bTBI has become an international problem in the field of neurotrauma research. Contributing to this problem is a lack of an experimental model that accurately mimics the characteristics of mild bTBI. To date, the “mild’’ versions of common experimental models of TBI have simply been less severe degrees of traumatic injury; these animals do not necessarily exhibit the clinical characteristics of mild bTBI seen in humans. Therefore, our first objective was to develop a highly controlled mouse model of bTBI using laser-induced shockwaves (LISWs). We established the parameters necessary to cause a reproducible injury of very mild severity, the most important feature seen in clinical practice. We defined very mild bTBI as having no traumatic change on the head visible to the naked eye after the insult was applied using very mild shockwaves to the heads of mice. Our very mild bTBI mouse model exhibited neurobehavioral changes in the chronic phase, such as cognitive impairment and depression-like behavior. We also observed an increase in 5-bromo-2′-deoxyuridine-positive, proliferating cells in the dentate gyrus during the acute phase and a subsequent decrease during the chronic phase. This model appears to be an accurate representation of the damage occurring in actual mild bTBI patients. We also found that an increase in cell proliferation in the dentate gyrus during the acute phase is the most prominent feature after a TBI.