The Cellular and Physiological Basis of Behavioral Health After Mild Traumatic Brain Injury

Depression and anxiety have been identified as the two common psychiatric symptoms of mild traumatic brain injury (TBI). These conditions are often comorbid with other symptoms such as post-traumatic headache and sleep disturbances, which can further exacerbate or be exacerbated by depression and anxiety. Although most preclinical investigations into the consequences of mild traumatic brain injury have focused on transient cognitive deficits, persistent changes in mental health have been receiving increasing attention. The research on cellular and physiological impact has primarily been conducted in adult male mice and rats; age and sex have been shown to be major factors in determining vulnerability to exhibiting these behavioral alterations. Cell death, axonal injury, inflammation, and neurotransmitter dysfunction have been proposed as potential mechanisms of behavioral dysfunction following TBI. As the cellular and molecular consequences of TBI are complex, these behavioral deficits most likely result as a combination of all of these changes. This chapter reviews the state of the literature on the establishment and utility of preclinical models of mild TBI to examine mechanisms of behavioral deficits in the chronic post-traumatic period.