Abstract
This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging 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. Pre-clinical PTSD was induced in naïve, 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 one hour 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 pre-frontal 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 pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. 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.
Highlights
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop in response to real or perceived life-threatening situations
We have shown that blocking certain downstream transcription factors and gene modifiers of these cytokines reduces oxidative stress, inflammation, and associated damage in hypertension, heart failure (HF), and metabolic syndrome (MetS)[6,7,16]
Oxidative Stress Analysis To investigate the influence of the predator exposure/psychosocial stress regimen on oxidative stress/redox balance, we examined levels of superoxide, peroxynitrite, and total reactive oxygen species (ROS) in the hippocampus, pre-frontal cortex (PFC), and adrenal glands
Summary
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop in response to real or perceived life-threatening situations. According to the Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-IV-TR), a diagnosis of PTSD necessitates exposure to a life-threatening event, intrusive recollections of the event, avoidance of associated stimuli and numbing of general responsiveness, hyperarousal not present before the trauma, and a significant social impairment. All of these symptoms must persist for at least 30 days[1]. We hypothesize that similar physiological mechanisms may play a role in PTSD development
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