Simultaneous Activation of Nrf2 and an Elevation of Dietary and Endogenous Antioxidants in Management of Post-Traumatic Stress Disorders and Traumatic Brain Injury

Abstract

Abstract: Despite animal and human studies and improved understanding of the symptoms and cellular damage, current managements of post-traumatic stress disorders (PTSDs) and traumatic brain injury (mild TBI and severe TBI) remain unsatisfactory. We identified three common biochemical defects increased oxidative stress, chronic inflammation and glutamate release that contribute to the initiation and progression of these diseases. Therefore, attenuation of these biochemical abnormalities may reduce the progression, and in combination with standard care, may improve the management of these neurological disorders. This review proposes that an elevation of the levels of antioxidant enzymes and phase-2-detoxifying enzymes, and dietary and endogenous antioxidants simultaneously is essential for attenuating oxidative stress, chronic inflammation, and glutamate release optimally. The levels of antioxidants can be increased by supplementation; however, an activation of a nuclear transcriptional factor Nrf2 and its binding with antioxidant response elements (AREs) is required for increasing the levels of antioxidant enzymes and phase-2-detoxifying enzymes. This review briefly discusses the regulation of Nrf2 activation, and identifies agents that activate Nrf2 by reactive oxygen species (ROS)-dependent and-independent mechanisms. Studies on the effects of individual antioxidants in PTSD and TBI are presented to show that the use of a single agent cannot activate Nrf2 and enhance the levels of dietary and endogenous antioxidants at the same time. The proposed mixture of micronutrients can achieve the above goal, and thereby, may reduce the progression, and in combination with standard care, improve the management of PTSD and TBI.