Role of Neurohumoral Imbalance at Post-Traumatic Stress Disorder in the Antitumor Immune Response. Experimental Study.

The aim of the study is to investigate the growth and development of B16 melanoma in mature male C57Black/6 mice with a post-traumatic stress disorder (PTSD) model. Behavioral, immunohistochemical, morphometric methods, enzyme immunoassay were used. A forced decrease in the level of corticosterone, which is characteristic for PTSD, was established, followed by intensification of the production of increased concentrations of pro-inflammatory interleukins by the cells of the immune system and, at the same time, a decrease in the secretion of anti-inflammatory cytokines. Priority data were obtained: the neurohumoral imbalance that develops in PTSD is a limiting factor to the growth of B16 melanoma, at least at the initial stages of the oncological process.

The Search for Diagnostic Criteria to Divide the Wistar Rat Population into Phenotypes during Modeling of Post-Traumatic Stress Disorder.

The levels of circulating hormones (corticosterone, testosterone, and leptin) and interleukins were studied in sexually mature male Wistar rats against the background of post-traumatic stress disorder (predator threat stress). It was found that in addition to the previously used anxiety index determined by animal behavior, the population of stressed individuals can be divided into stress-resistant and stress-sensitive phenotypes by the level of leptin and the index of anabolism (testosterone/corticosterone ratio). For the first time, it was determined that in stress-resistant rats, the levels of leptin and the testosterone/corticosterone index exceeds the control values, while in stress-sensitive individuals, these indicators are much lower.

Phenotypically Determined Liver Dysfunction in a Wistar Rat Model of Post-Traumatic Stress Disorder.

The extraordinary situation of the 2019-2022 pandemic caused a dramatic jump in the incidence of post-traumatic stress disorder (PTSD). PTSD is currently regarded not only as a neuropsychiatric disorder, but also as a comorbidity accompanied by cardiovascular diseases, circulatory disorders, liver dysfunction, etc. The relationship between behavioral disorders and the degree of morphofunctional changes in the liver remains obscure. In this study, PTSD was modeled in sexually mature male Wistar rats using predatory stress induced by a prey's fear for a predator. Testing in an elevated plus maze allowed the rat population to be divided into animals with low-anxiety (LAP) and high-anxiety (HAP) phenotypes. It was found that morphofunctional analysis of the liver, in contrast to its biochemical profiling, provides a clearer evidence that predatory stress induces liver dysfunction in rats of both phenotypes. This may indicate a decrease in the range of compensatory adaptive reactions in stressed animals. However, in HAP rats, the level of morphofunctional abnormalities in the mechanisms responsible for carbohydrate-fat, water-electrolyte and protein metabolism in the liver testified the prenosological state of the organ, while further functional loading and resulting tension of the regulatory systems could lead to homeostatic downregulation. Meanwhile, the liver of LAP animals was only characterized by insignificant diffuse changes. Thus, we demonstrate here a link between behavioral changes and the degree of morphofunctional transformation of the liver.

Indicators of Hypoxia Tolerance as Determined by Cellular Elements of Rat Blood.

Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors' choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the "rise to an altitude" of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger.

For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.

Analysis of Healing of Rat Uterine Wall After Full-Thickness Surgical Incision.

We studied the dynamics of morphological changes in the operated segment of the uterine horn of Sprague-Dawley rats during the first 2 weeks of the wound-healing process after a full-thickness surgical incision with regard to the estrous cycle phase. Morphometric parameters of injured uterine right horn were compared with those in the intact left horn of the same animal as a control of changes determined by the hormonal background. It was found that the uterine epithelium in the focus of injury was restored as soon as on day 2 after surgery under the influence of estrous cycle hormones. By day 4, the wound space was completely filled with the endometrial tissue on the side of the uterine lumen and coved by the attached adipose tissue of the mesentery on the side of the abdominal cavity. The thickness of the uterine wall and the uterine lumen differed most strongly between the operated and intact uterine horns during the first 3 days and on day 6 after surgery. The size of the healing area increased during the first three days and reached the peak value by day 3, but then decreased to minimum by day 6.

Comparison of the Adaptive Capacity in Old and Young Wistar Rats to Stress Exposure and Acute Hypoxic Hypoxia.

We compared behavioral and psychoemotional manifestations of young and old male Wistar rats in elevated plus-maze, the levels of corticosterone and testosterone, as well as the resistance to acute hypoxic hypoxia before and after stress exposure (10-min swimming sessions over 10 days). The behavioral characteristics, responses of the main stress hormone corticosterone, and resistance to acute hypoxic hypoxia were identical in both age groups before and after stress. A distinguishing feature was pronounced flattening of the psychoemotional manifestations in old animals. The main adaptive differences between young and old rats were revealed in the response of circulating testosterone to stress.

Ultradian Biorhythms of C57BL/6 Mice Body Temperature under Constant Illumination or during Natural Day-Night Cycle.

The study analyzed the dynamics of intraperitoneal body temperature in C57BL/6 mice during 39 days of uninterrupted measurements. When mice were exposed to constant illumination, the ultradian oscillations of body temperature demonstrated the rhythms with periods of 2 h, 60 min, and 12 min, which were the higher harmonics of the circadian temperature oscillations. In two mutually isolated groups exposed to constant illumination, the phases of revealed biorhythms coincided. When the mice maintained under natural illumination, the body temperature demonstrated the ultradian rhythms with the same periods, which indicated that constant illumination did not distort the parameters of ultradian biorhythms. Probably, there is an external biotropic factor with similar harmonic spectrum, which synchronizes these biorhythms.