Stress is known to affect the intensity of the immune response. The involvement of central regulatory structures in mediating these changes was addressed by analyzing the extent of activation of neurons in the hypothalamus (in terms of the number of c-Fos-positive cells) in rats 2 h after i.v. administration of lipopolysaccharide alone and on the background of electrical pain stimulation. Studies were performed using 52 male Wistar rats weighing 200-250 g. c-Fos protein expression was studied by immunohistochemical analysis. Increases in the quantity of c-Fos-positive cells 2 h after administration of lipopolysaccharide were seen in the following hypothalamic structures: AHN, PVH, LHA, VMH, DMH, and PH. After electrical pain stimulation, the number of c-Fos-positive cells increased in these same hypothalamic structures (AHN, PVH, LHA, VMH, DMH, and PH). The combination of electrical pain stimulation and lipopolysaccharide administration led to a decrease in the extent of activation in hypothalamic structures AHN, PVH, LHA, and VMH as compared with the characteristic reaction to lipopolysaccharide without electrical pain stimulation. Electrical pain stimulation suppressed the intensity of the immune response induced by lipopolysaccharide (as assessed by local hemolysis and counts of the numbers of spleen antibody-forming cells). Thus, changes in the extent of activation of hypothalamic structures (AHN, PVH, LHA, VMH) correlated with the development of stress-induced immunosuppression, i.e., morphofunctional mapping of the extent of activation of hypothalamic structures allowed identification of which changes in hypothalamic cell activity occurred with stress-induced changes in immune system responses to antigen administration.
Application of different stimuli activated different hypothalamic structures. Immunohistochemical methods demonstrated changes in the numbers of c-Fos-positive cells in various hypothalamic structures after electrical pain stimulation and i.v. administration of antigens (bovine serum albumin (BSA) and lipopolysaccharide (LPS)). Increases in the numbers of c-Fos-positive cells in all the hypothalamic structures studied occurred after electrical pain stimulation and i.v. administration of antigens (BSA and LPS). The highest level of activation in hypothalamic structures was seen in the anterior hypothalamic nucleus (AHN) and posterior hypothalamic area (PH) after electrical pain stimulation and in the paraventricular nucleus (PVN) and lateral hypothalamic area level 28 (LHA-28) after i.v. administration of LPS. Comparative analysis showed that the level of activation of hypothalamic structures after electrical pain stimulation was significantly greater in the AHN, PVN, LHA, and PH than after i.v. administration of antigens (LPS and BSA). Administration of LPS led to more marked activation of cells in hypothalamic structures APH, PVN, LHA-28, dorsomedial hypothalamic nucleus (DMH), and PH (in terms of the numbers of c-Fos-positive cells) than administration of BSA.
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