Simultaneous Activation of Nrf2 and Elevation of Antioxidant Chemicals in Management of Post-Traumatic Stress Disorders and Traumatic Brain Injury.

Prasad, Kedar N.

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 penetrating TBI) remain unsatisfactory. Despite differences in etiology and symptoms, three common biochemical defects increased oxidative stress; chronic inflammation and glutamate release that contribute to the initiation and progression of these diseases were identified. 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 optimally attenuating oxidative stress, chronic inflammation, and glutamate release. The levels of antioxidants are 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 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 simultaneously. The proposed micronutrient cocktail can achieve the above goal, and thereby, may reduce the progression, and in combination with standard care, improve the management of PTSD and TBI.

Balkan Military Medical Review, 2015, Vol 18, Issue 4, p116

1107-6275

Academic Journal

10.5455/bmmr.181002