Sex-Related Features of the Reactions of Microcirculation Parameters in Symmetrical Areas of the Human Head to Hypoxic Exposure.

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.

Lymphocyte Index of Peripheral Blood in Rats at Different Stages of the Post-Stress Period under Conditions of Antigenic Exposure and Injection of Lipopolysaccharide.

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.

Analysis of Changes in Microcirculation Parameters of Symmetrical Areas of the Human Head under Conditions of Hypoxic Influences.

The reactions of microcirculation parameters of symmetrical areas of the human head to hypoxic loads were studied. The study was conducted in 10 healthy male volunteers aged 18-19 years. Short-term hypoxia was modeled using a ReOxy Cardio normobaric device (S. A. Aimediq). Synchronous measurements of microcirculation parameters in symmetrical temporal regions of the head at the basal state and immediately after short-term hypoxic exposure were carried out by the method of laser Doppler flowmetry. We evaluated statistical characteristics of perfusion of both sides, as well as regression characteristics of the relationship between changes in the microcirculation parameters and the initial values of these parameters. It was shown that the reaction of the microcirculation parameters in symmetrical regions of the head to hypoxia depends on the initial microcirculation parameters in ipsi- and contralateral sides. 3D graphs were constructed and regression equations describing these relationships were formulated. A new method of geometric sensing is proposed, which allows predicting the direction of reactions to hypoxic effects. The obtained data illustrate the specificity of regulation of microcirculation of paired organs determined by the presence of functional asymmetry. A new method of geometric zoning is proposed, which allows solving the problems of personalized assessments of the state of the microcirculation system in patients.

Blood Cytokine Concentration in Rats during Antigenic Treatment after a Single Long-Term Stress Exposure.

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-1ß 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-1ß) 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.

State of Stress-Marker Organs in Rats after a Single Exposure to Long-Term Stress and Treatment with Lipopolysaccharide.

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.

Blood Cytokine Profile in Rats with Various Behavioral Characteristics after a Single Exposure to Long-Term Stress.

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.

Cytokine levels in rat blood and brain structures after administration of lipopolysaccharide.

We compared cytokine profile of rat serum and brain structures after immune status modulation by LPS (30 µg/kg intraperitoneally). The content of inflammatory (IL-1α, IL-1ß, IL-2, IL-6, IFN-γ, and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines in biological samples of animals was measured on days 1 and 7 after antigenic stimulation. LPS administration reduced the levels of both inflammatory and anti-inflammatory cytokines in the peripheral blood of the rats, especially on the 1st day. LPS administration was also accompanied by specific changes in cytokine content in the dorsal hippocampus and anterior cingulate cortex. Antigenic stimulation increased the level of anti-inflammatory cytokines IL-4 and IL-10 in the examined brain tissues, the changes were most pronounced on day 1 after LPS injection. No significant changes in the levels of proinflammatory cytokines in the brain tissue of animals were found at the above terms after LPS injection. Thus, peripheral LPS administration to rats shifts the balance between the inflammatory and anti-inflammatory cytokines in the CNS structures towards the latter.

Nociceptive thresholds in rats in response to lipopolysaccharide injection into the specific nuclei of the thalamus of the brain.

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.

Nociceptive sensitivity and lymphocytic index of peripheral blood in rats with different behavioral activity in model of inflammatory pain provoked by injection of freund's complete adjuvant and bovine serum albumin.

Nociceptive thresholds decreased in rats at the early stage of inflammatory reaction induced by subcutaneous injection of BSA and complete Freund's adjuvant. At the later stage of this reaction, there was a trend of restoring nociceptive parameters in behaviorally passive rats in contrast to active animals, which demonstrated further decrease in the nociceptive thresholds. During the late inflammatory period, the lymphocytic index (by Shaganin) changed unidirectionally in the rats with different behavioral parameters. Probably, the changes in nociceptive thresholds were not triggered by the shift in lymphocyte/segmented neutrophil ratio, but resulted from production of yet not established biologically active agents with proalgesic and analgesic nature.

Nociceptive thresholds of the response to lipopolysaccharide injection into the limbic structures of the brain in rats.

Microinjections of LPS into the limbic structures of rat brain (dorsal hippocampus and caudal compartment of the cingulate fascicle) caused opposite effects on the nociceptive thresholds: injection into the dorsal hippocampus enhanced perception and reduced the emotional affective perception of pain, while injection into the cingulate fascicle reduced the perceptual and enhanced the emotional components of the nociceptive reaction. These results indicated specific involvement of these limbic structures in nociception modulation during induction of the immune response in CNS.

Study of the cognitive component of nociception by the tail flick method.

The possibility of using the tail flick test as a model for studies of the cognitive component of nociception in rats was evaluated. The results were compared with the data of active avoidance test in a shuttle chamber. The results demonstrate the methodological potentialities of the tail flick test as a convenient model for training of animals in studies of the nociceptive reactions.

Role of caudomedial portion in left and right cingulum bundle in perceptual and emotional components of nociception in rats.

The effects of electrocoagulation of caudomedial portion of the left and right cingulum bundles on tail-flick latency and vocalization threshold were examined on rats. We revealed a tendency to a decrease in the tail-flick latency and more pronounced elevation of the vocalization threshold after destruction of the right cingulum bundle. These findings indicate functional asymmetry of the cingulum bundle in the realization of the emotional nociceptive reaction.