The role of the stress system in recovery after traumatic brain injury: A tribute to Bruce S. McEwen.

Traumatic brain injury (TBI) represents a major public health concern. Although the majority of individuals that suffer mild-moderate TBI recover relatively quickly, a substantial subset of individuals experiences prolonged and debilitating symptoms. An exacerbated response to physiological and psychological stressors after TBI may mediate poor functional recovery. Individuals with TBI can suffer from poor stress tolerance, impairments in the ability to evaluate stressors, and poor initiation (and cessation) of neuroendocrine stress responses, all of which can exacerbate TBI-mediated dysfunction. Here, we pay tribute to the pioneering neuroendocrinologist Dr. Bruce McEwen by discussing the ways in which his work on stress physiology and allostatic loading impacts the TBI patient population both before and after their injuries. Specifically, we will discuss the modulatory role of hypothalamic-pituitary-adrenal axis responses immediately after TBI and later in recovery. We will also consider the impact of stressors and stress responses in promoting post-concussive syndrome and post-traumatic stress disorders, two common sequelae of TBI. Finally, we will explore the role of early life stressors, prior to brain injuries, as modulators of injury outcomes.