The parameters of the cytokine profile and functional activity of the complement system in the blood of rats were studied during different time periods of chronic unpredictable mild stress using a model of sequentially alternating low-intensity stress effects for 1, 2, 3, and 4 weeks. In the dynamics of observation, a general tendency towards multidirectional fluctuations in the concentration of cytokines was revealed: an increase in IL-10, but a decrease in IL-4 in comparison with the control. Statistically significant changes in the level of IL-10 were noted after 2, 3, and 4 weeks, IL-4 — after 2 and 4 weeks of stress loads. The percentage of lysis of the C3 component in rats gradually increased by the 2nd week of chronic stress, but then decreased and practically did not differ from the control values (intact animals) by the end of the study. These results illustrate the specificity of changes in the indicators of the C component of the complement system and the cytokine profile of the blood reflecting activity of the cellular and humoral components of the immune response in rats exposed to repeated stress factors of different origins and duration.

Длительные стрессорные воздействия вызывают дизрегуляцию большинства компонентов иммунной системы. Большой интерес исследователей к изучению системы комплемента и цитокинов связан с широким спектром их функций. Цель исследования – изучение показателей концентрации цитокинов и функциональной активности системы комплемента в крови крыс на модели хронического непредсказуемого мягкого стресса разной длительности. Методы. Исследование проведено на 42 крысах-самцах Wistar. Выделены 5 экспериментальных групп: контрольная группа; четыре опытные группы, которых подвергали многократным стрессорным нагрузкам на модели хронического непредсказуемого мягкого стресса в течение 1, 2, 3 и 4 недель соответственно. Концентрацию ИЛ-4 и ИЛ-10 в сыворотке крови крыс определяли методом твердофазного ИФА, функциональную активность системы комплемента – с помощью скрининг-теста в реакции комплемент-зависимого лизиса эритроцитов человека. Результаты. Выявлено статистически значимое повышение уровня ИЛ-10 через 2, 3 и 4 недели, но снижение концентрации ИЛ-4 в крови крыс через 2 и 4 недели стрессорных воздействий. Функциональная активность системы комплемента увеличивалась через 2 недели хронического стресса, но не отличалась от контрольных значений в последующие периоды. Заключение. Выявленные изменения иллюстрируют специфику активности клеточного и гуморального звеньев иммунного ответа в условиях многократных непредсказуемых стрессорных воздействий разной длительности. Long-term stress causes dysregulation of most components of the immune system. The great interest of researchers in studying the complement system and cytokines is associated with a wide range of their functions. The purpose of the study was to study the concentrations of cytokines and the functional activity of the complement system in the blood of rats using a model of chronic unpredictable mild stress of different durations. Methods. The study was conducted on 42 male Wistar rats. There were 5 experimental groups: control group; four experimental groups that were subjected to repeated stress loads in a chronic unpredictable mild stress model for 1, 2, 3 and 4 weeks, respectively. The concentration of IL-4 and IL-10 in the blood serum of rats was determined by solid-phase enzyme immunoassay, the functional activity of the complement system was determined using a screening test in the reaction of complementdependent lysis of human erythrocytes. Results. A statistically significant increase in the level of IL-10 was revealed after 2, 3 and 4 weeks, but a decrease in the concentration of IL-4 in the blood of rats after 2 and 4 weeks of stress exposure. The functional activity of the complement system increased after 2 weeks of chronic stress, but did not differ from control values in subsequent periods. Conclusion. The identified changes illustrate the specificity of the activity of the cellular and humoral components of the immune response under conditions of repeated unpredictable stressors of varying duration.

In this study, we conducted a comparative analysis of the responses to hypoxia of microcirculation (MCR) parameters of the temporal areas of the head in male and female subjects. The study was conducted in 20 healthy volunteers aged 18–19 (10 male and 10 female). The state of short-term hypoxia was induced using a ReOxy Cardio normobaric device (S.A. Aimediq, Luxembourg). Synchronous measurements of MCR parameters of symmetrical temporal regions of the head in the basal state and immediately after short-term hypoxic exposure were carried out by laser Doppler flowmetry. Statistical characteristics of perfusion of both sides of the measurement and correlation characteristics of the relationships between changes in the MCR parameters of the symmetric sides of the observation were evaluated. The results show sex differences in reactions to hypoxic effects. In 80% of men, hypoxia led to an increase in left perfusion; in 20%, to a decrease. In women, the opposite pattern was observed: in 10%, perfusion on the left increased, and in 90%, it decreased. The results of the research revealed the features of left–right asymmetry in the regulation of MCR parameters of the temporal regions of the heads of males and females. The physiological mechanisms underlying the differences in the regulation of MCR parameters of the symmetrical regions of the male and female brain require further study.

Purpose. To study the effect of short-term hypoxic exposure on correlation between microcirculatory parameters (MCR) of symmetric areas of the human head. Materials and methods. MCR parameters of 10 healthy male volunteer were measured by laser Doppler flowmetry method. Short-term hypoxic exposure was produced according to the hypoxic test method using the ReOxy Cardio unit (S. A. Aimediq). We assessed the perfusion metrics left and right areas of interest, neurogenic, myogenic, respiratory and cardiac contributors to vascular tone and correlations between baseline parameters and after hypoxic exposure. Results. We revealed the specificity of regional circulation system rearranging induced by hypoxic load. The specificity is caused by functional asymmetry of correlations between different vascular tone contributors in symmetrical head areas. Strong correlation declining under the hypoxic loads between baseline perfusion on left/right was found. The perfusion changes of symmetrical temporal areas under the hypoxic loads correlate negatively with the baseline perfusion of both the same and the opposite side. Conclusion. Short-term hypoxic load rearranges the balance of different vascular tone contributors regulatory role in MCR of symmetric head areas to maintain the sustainable activity of the whole MRC.

— A new computational and experimental method for assessing the stability of oscillatory processes occurring in the microcirculation (MCR) system is proposed. The technique is based on the analysis of the stability of a differential equations system describing fluctuations in the MCR parameters of blood in symmetrical temporal head regions of humans. Using this technique, we have investigated the change in the stability of MCR parameters of the symmetrical temporal head regions under hypoxic conditions. The study has involved 10 healthy male volunteers (18–19 years). The state of short-term hypoxia has been induced using a normobaric ReOxy Cardio device (S.A. Aimediq, Luxembourg) certified in the Russian Federation for obtaining hypoxic and hyperoxic gas mixtures based on biofeedback with a built-in pulse oximetric sensor (Masimo Rad-5, United States). Synchronous measurements of MCR parameters of symmetrical temporal head regions at the basal state and immediately after short-term hypoxic exposure have been carried out by the method of laser Doppler flowmetry (LDF) using a two-channel LAKK–02 device (LAZMA Research and Development enterprise, Russia). It has been shown that short-term hypoxic effects change the numerical values of the stability parameters in all subjects within the boundaries of stability levels. However, the response to hypoxic exposure has been very individual in different subjects. The proposed method allows for personalized assessments of the fitness level and resistance to hypoxic influences in different subject groups.

We studied sex-related features of the microcirculation response of symmetrical areas of the human head to hypoxic loads. In 20 healthy volunteers (10 male and 10 female), short-term hypoxia was modeled using the ReOxy Cardio device (S. A. Aimediq). Microcirculation parameters were synchronously measured by laser Doppler flowmetry in the initial state and immediately after short-term hypoxic exposure. 3D graphs were constructed and regression equations were formulated that describe the relationships between changes in microcirculation on both sides of the measurement. Using a new method of geometric zoning, it was shown that the direction of reactions to hypoxia of the left microcirculatory bed is opposite in subjects of different sexes. In 80% male subjects, hypoxia led to an increase in perfusion on the left, in 20% - to a decrease. In female subjects, the picture was opposite: perfusion decreased in 90% and increased in 10% subjects. It can be assumed that these differences in the reactions of microcirculation to hypoxia in men and women are an additional confirmation of different structural and functional organization of the male and female brain, which leads to different resistance of males and females to external disturbing influences. The results of the study can be used in medical practice to develop methods for personalized assessments of circulatory disorders and differentiated approaches to the treatment of men and women with cardiovascular diseases.

Changes in the Shaganin lymphocyte index (ratio of the number of lymphocytes to segmented neutrophils) in the peripheral blood of rats after intraperitoneal administration of LPS (100 μg/kg) at the end of a single stress exposure in a model of 24-h restraint stress were studied. The lymphocyte index was analyzed 3 h later, on the 1st and 8th days after the stress load. Immobilization was accompanied by a decrease in this parameter 3 h after exposure. One day after the stress load, an increase in the lymphocyte index was noted, which remained on the 8th day of observation. LPS injection did not affect the changes in this parameter caused by 24-h immobilization on the 1st and 8th days of the study, but prevented a pronounced increase in the lymphocyte index on the 1st day after the stress load. The data obtained expand the existing scientific understanding of the specificity of the involvement of immunomodulatory substances in the implementation of adaptive-compensatory processes in mammals under conditions of emotional stress.

Острую воспалительную боль относят к самостоятельной форме боли. Выявлен ряд факторов ее возникновения, среди которых: иммунные клетки, цитокины, простагландины, различные патогенные микроорганизмы и другие. Установлены пути и механизмы активации ноцицепторов при остром воспалении. Определены некоторые пути нейроиммунных взаимодействий в очаге воспаления. Результаты экспериментальных и клинических исследований в области алгологии перспективны в плане разработки новых методов лечения и предотвращения развития острой воспалительной боли.

The dynamics of parameters for the intensity of metabolic processes in rats was studied after intraperitoneal injection of lipopolysaccharide (LPS, 100 µg/kg) by the end of a single exposure to long-term stress on the model of 24-h immobilization. The volumes of consumed oxygen and expired carbon dioxide, as well as the level of heat emission, were evaluated on a Phenomaster automated module device (TSE Systems GmbH, Germany) 3 h and 1 or 8 days after the treatment. Study parameters of metabolism in animals of the physiological saline group were shown to increase significantly 1 day after restraint stress. The observed variations illustrate intensification of metabolic processes in rats during the early period after experimental stress. These changes persisted even in the delayed stage after stress load (day 8 of observations). The specimens receiving LPS were characterized by a rise in oxygen consumption, carbon dioxide expiration, and level of heat exchange on day 1 of the post-stress period. On day 8 after stress load with the subsequent immune modulation, metabolic parameters in rats were revealed to decrease and did not differ from those in intact animals. Therefore, the antigenic treatment by systemic administration of LPS has no effect on a stress-induced activation of metabolic processes at the early stage of observations, but prevents a persistent increase in the intensity of metabolism during the delayed post-stress period. Our results and published data suggest that the influence of LPS, which possesses immunoactive properties, is related to the modulatory effect on neuroendocrine mechanisms for regulation of homeostasis in mammals, e.g., under stress conditions.

We studied changes in the blood cytokine profile of rats 3 h, 1 day, and 8 days after acute stress on the model of 24-h immobilization followed by LPS administration (100 μg/kg intraperitoneally). The concentration of proinflammatory cytokines (particularly of IL-1β and TNFα) significantly decreased at the early stage after stress exposure and physiological saline injection, but increased in the follow-up period and practically did not differ or even surpassed the control level by the end of observations. Under these conditions, the blood content of anti-inflammatory cytokine IL-10 increased most significantly on day 1 of the post-stress period. Restraint stress followed by LPS administration was accompanied by a decrease in the level of proinflammatory cytokines at the early (IFNγ and TNFα) and late stages (IL-1β) of the experiment. Directed modulation of the immune status in animals after acute stress was followed by a significant increase in the content of IL-10 on days 1 and 8, as well as by a tendency toward elevation of IL-4 concentration by the end of the study. The directionality and degree of changes in the cytokine profile of mammalian tissues depend on the type of extreme exposure, duration of the post-stress period, and specific effects of exogenous pathogenic factors in the whole body.

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 μg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

Changes in the blood cytokine profile of rats with different behavioral activity were evaluated in various periods after stress exposure on the model of 24-h immobilization. Behaviorally active animals exhibited only a tendency to a change in the concentration of study cytokines in the dynamics after experimental stress. Stress exposure in passive specimens was accompanied by a decrease in the content of pro- and anti-inflammatory cytokines. These changes were most pronounced at the early stages of the post-stress period and persisted until the end of observations. After a single exposure to long-term immobilization, cytokine level in the peripheral blood of behaviorally passive animals was much lower than in active rats. Variations in immune indexes of mammals depend on the initial parameters of their behavior and duration of the post-stress period. Differences in the blood cytokine profile during negative emotiogenic exposures in passive and active rats are probably related to the specifics of immune reactivity in specimens with various sensitivities to stress.

Microinjections of LPS into the specific nuclei of rat thalamus (ventrobasal thalamic nuclei VPL and VPM) slightly increased perceptual component and significantly decreased emotional component of systemic nociceptive response.