Lessons Learned from Behavioral and Molecular Characterization of Chronic Preclinical TBI

Abstract

As many as 30% of Veterans have suffered traumatic brain injury (TBI). Even with mild TBI (mTBI), the effects of the injury can be detrimental to the Veteran’s quality of life. Persistent symptomology can include psychological, motor, and visual deficits. This is especially true with repetitive mTBI (rmTBI). We have been endeavoring to establish a preclinical model of chronic rmTBI to allow for the study of diagnostic and therapeutic protocols. We have used both open-head (surgical) and closed-head injury models and characterized them behaviorally and molecularly. Behavioral analyses assessed anxiety (elevated plus maze, open field test), depression level (forced swim test), spatial learning and memory (Morris water maze and Barnes maze), recognition memory (novel object recognition), and locomotor ability (rotarod, open field test). RNA-seq was used to look for a blood molecular signature for rmTBI. This talk will share data we have collected along this journey, what we think the data indicates, and the challenges we have yet to overcome.