Emotional and somatic disturbances following mild traumatic brain injury

Abstract

Two of the most common symptoms following mild traumatic brain injury (mTBI) are post-traumatic headache (PTH) and depression, yet these symptoms are understudied in preclinical literature. Research has suggested a link between depressive symptoms and altered dopamine signaling and between PTH and depression. To study these connections, I first used male and female mice in a model of single mTBI and evaluated them for depressive-like behavior using the forced swim and tail suspension tests, changes in post-traumatic pain using von Frey testing, and evoked dopamine signaling using in vivo fast scan cyclic voltammetry. I found that at 4 and 8 weeks post-injury, brain-injured female mice had an increase in post-traumatic pain, and male brain-injured mice had an increase in depressive behavior in the forced swim test and displayed increased evoked extracellular dopamine following cocaine inhibition of the dopamine transporter. These results suggest changes in dopamine kinetics and signaling in brain-injured male mice which may explain the observed increase in depressive-like behavior; additionally, dopamine signaling does not appear to influence onset of PTH in mice following mTBI. Athletes represent a population of people who are at risk for sustaining repetitive mild traumatic brain injuries (rmTBI) in a short amount of time. A large number of studies have shown that exercise strengthens the brain, yet no studies utilize exercised animals, instead only using exercise as a therapeutic intervention. In the second part of the project, I used a model of rmTBI in both exercised and unexercised mice to examine the effect of pre-injury exercise on development of depressive-like behavior and facial allodynia. I observed that rmTBI decreased depressive-like behavior and increased threshold of periorbital mechanical stimulation in brain injured male mice. In brain-injured female mice, rmTBI decreased time immobile compared to sham injured female mice, and periorbital threshold in unexercised female mice decreased over time. These results are contrary to previously published reports, and this may be due to methodological issues. However, these results demonstrate the sex-specific effects of rmTBI on development of both emotional and physical symptoms, and this study provides the groundwork for continuing studies using exercised mice as a more relevant model of athlete rmTBI.%%%%M.S., Neuroscience – Drexel University, 2015