Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

Abstract

Traumatic stress may chronically affect master homeostatic systems at the crossroads of peripheral and central susceptibility pathways and lead to the biological embedment of trauma-related allostatic trajectories through neurobiological alterations even decades later. Lately, there has been an exponential knowledge growth concerning the effect of traumatic stress on oxidative components and redox-state homeostasis. This extensive review encompasses a detailed description of the oxidative cascade components along with their physiological and pathophysiological functions and a systematic presentation of both preclinical and clinical, genetic and epigenetic human findings on trauma-related oxidative stress (OXS), followed by a substantial synthesis of the involved oxidative cascades into specific and functional, trauma-related pathways. The bulk of the evidence suggests an imbalance of pro-/anti-oxidative mechanisms under conditions of traumatic stress, respectively leading to a systemic oxidative dysregulation accompanied by toxic oxidation byproducts. Yet, there is substantial heterogeneity in findings probably relative to confounding, trauma-related parameters, as well as to the equivocal directionality of not only the involved oxidative mechanisms but other homeostatic ones. Accordingly, we also discuss the trauma-related OXS findings within the broader spectrum of systemic interactions with other major influencing systems, such as inflammation, the hypothalamic-pituitary-adrenal axis, and the circadian system. We intend to demonstrate the inherent complexity of all the systems involved, but also put forth associated caveats in the implementation and interpretation of OXS findings in trauma-related research and promote their comprehension within a broader context.

New Metabolic, Digestive, and Oxidative Stress‐Related Manifestations Associated with Posttraumatic Stress Disorder

“…Several animal models involving rats postulated that a prolonged exposure to stress leads to increased ROS levels in certain regions of the brain, namely, the prefrontal cortex and the hippocampus. Scientists also observed features such as weight gain, a higher body temperature, and changes in the liver and heart histopathology depicting tissues with inflammation and fibrosis [ 98 ]. They also found a significant level of OXS-related proteins in plasma, as well as a high inflammation state.…”

Cycloastragenol, a Triterpenoid Saponin, Regulates Oxidative Stress, Neurotrophic Dysfunctions, Neuroinflammation and Apoptotic Cell Death in Neurodegenerative Conditions

“…Several studies have strongly unveiled the role of Nrf2 in the pathophysiology of AD-related neurodegeneration [5,6]. Elevated oxidative stress is responsible for the dysregulation of several physiological phenomena in the central nervous system, such as neurogenesis, inflammatory mediators, and mitochondrial homeostasis [7]. The hippocampus possesses the most unique characteristic of neuronal cells renewal, called adult hippocampal neurogenesis (AHN), which continues throughout the life of an individual [8], providing neural plasticity to the hippocampus [9].…”

Association of adverse childhood experiences with the development of multiple sclerosis

“… 7 25 The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation. Childhood abuse can cause dysregulation of the hypothalamic–pituitary–adrenal axis, 26 lead to oxidative stress 27 and induce a proinflammatory state decades into adulthood. 28 Psychological stress has been shown to disrupt the blood–brain barrier 29 and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS. 30 Neonatal emotional and physical stress increased the susceptibility and severity of MS-like disease in mice, due to downregulation of adrenergic receptors in innate immune cells.…”