Development and Characterization of a Closed-Head Mild Traumatic Brain Injury Model

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and places an enormous economic burden on both families and health care systems that provide support for survivors. The majority of TBI cases are deemed mild (mTBI) and go undetected due to the less discernable signs and symptoms. However, there is increasing evidence that mTBI can lead to detrimental chronic consequences. Unfortunately, the mTBI research field is still in its infancy. We set out to develop a model of closed-head mTBI that recapitulated mTBI in the clinic. Using a murine controlled cortical impact model, we show no structural damage, increased edema, behavioral deficits, cell death and decreased synapses in the acute time after the mTBI. We also evaluated the chronic behavioral changes from two weeks to three months post TBI. All in all, our mTBI model showed significant cellular changes, but did not give robust chronic behavioral results. A secondary outcome of our study was the evaluation of a potential therapeutic: remote ischemic conditioning (RIC). Acutely, RIC improved edema, behavioral outcomes, cell death, and synapse loss. Overall, our study does identify key areas that should be recapitulated in further development of the model: no structural damage, little to no edema, cell death and decreased synapses, and behavioral changes. This model also requires further investigation into the chronic consequences of mTBI as well as the use of RIC.