Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

Abstract

Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC’s ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC’s reduction of oxidative stress.

Paradoxical Anxiety Level Reduction in Animal Chronic Stress: A Unique Role of Hippocampus Neurobiology

“…For the PSS protocol, rats were exposed to cat urine scent in a Petri dish with litter for 10 min daily for 10 days (21 rats were submitted to stress exposure; 8 control rats were exposed to a neutral scent). Repeated exposure to the PSS may be a more accurate model of human PTSD than a single acute exposure approach, granted that it minimizes the effect of confounding factors, such as the concentration of pheromones in each individual urine scent exposure [ 54 ]. All procedures were performed between 1:00 and 2:00 p.m. During the scent exposure protocol, stress-related behavior was captured daily via a web camera.…”

“…All procedures were performed between 1:00 and 2:00 p.m. During the scent exposure protocol, stress-related behavior was captured daily via a web camera. Behavioral evaluation was conducted via the 3D animal tracking system “EthoStudio” [ 18 , 54 ]. The evaluator of the behavior had not previously worked with any rats in our groups.…”

Adaptation to Hypoxia: A Chimera?

“…Intermittent hypoxic conditioning (IHC) is a promising approach to induce protection in several different tissues. Manukhina et al [10] tested whether 14-day IHC, in addition to the known cardio-, vaso-, and neuroprotective effects, may also alleviate post-traumatic stress disorder, which causes mental and somatic diseases. IHC has favorable effects at several levels, including the anxiety index and the associated reduced glycogen content in the heart and liver, with reduced histological signs of metabolic and hypoxic damage and of impaired contractility.…”

Intermittent Hypoxic Training as an Effective Tool for Increasing the Adaptive Potential, Endurance and Working Capacity of the Brain

“…IHT also has a direct effect on brain function and was shown to improve cerebral blood flow ( Steinback and Poulin, 2016 ), protect cerebrovascular function ( Manukhina et al, 2016 ), strengthen brain connectivity and increase its hypoxia tolerance ( Li et al, 2016 ). Moreover, IHT can reduce oxidative stress caused by post-traumatic disorders at the level of carbonylated proteins and lipid peroxidation products ( Manukhina et al, 2020 ). IHT has also been shown to suppress the cytotoxic signaling cascades activated by excess glutamate induced by ethanol withdrawal in the rat, preventing p30 activation and down-stream increase of presenilin 1 (PS1), Aβ1–40 and Aβ1–42 content in the prefrontal cortex of rats ( Ryou et al, 2017 ).…”