Severe life stress and oxidative stress in the brain: from animal models to human pathology

Significance. Severe life stress (SLS), as opposed to trivial every day stress, is defined as a serious psychosocial event with the potential to cause an impacting psychological traumatism. Recent Advances. Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues. In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods to measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, caused by traumatic events such as child abuse, war and divorce, is also accompanied by oxidative stress in the CNS. Future Directions. Outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining sources of oxidative stress in SLS might on the long run provide new therapeutic avenues.