Inflammation and Oxidative Stress in the Brain and Blood in an Animal Model of Post-Traumatic Stress Disorder: Mechanisms for PTSD Progression

Abstract

We sought to analyze specific pathophysiological mechanisms involved in the progression of posttraumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Preclinical PTSD was induced in naive male Sprague–Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized, and their brains were dissected to remove the hippocampus, amygdala, and prefrontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of proinflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group versus controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems. List of Abbreviations ACTH Adrenocorticotropic hormone ANOVA Analysis of variance AVP Arginine vasopressin cDNA Complementary DNA CIITA Class II major histocompatibility complex transactivator CMH 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine CNS Central nervous system CO2 Carbon dioxide *Email: jfrancis@vetmed.lsu.edu Comprehensive Guide to Post-Traumatic Stress Disorder DOI 10.1007/978-3-319-08613-2_87-1 # Springer International Publishing Switzerland (outside the USA) 2015