Postresuscitation Changes in Neuronal Hippocampal Populations in Rats with Different Learning Ability

The state of pyramidal cell populations in CA1 and CA4 hippocampal fields was studied in resuscitated and intact rats with different learning ability. Morphometry showed that postresuscitation damage to neurons was more pronounced in good learners compared to poor learners. Interferometry revealed higher protein content in neurons in poor learners compared to successfully trained rats. It was hypothesized that different neuronal resistance to ischemia in rats characterized by different learning ability is determined by some peculiarities in protein metabolism preexisting in intact animals and manifesting in the postresuscitation period.     

Cl<Superscript>−</Superscript> conduction of GABA<Subscript>A</Subscript>-receptor complex of synaptic membranes of rat brain cortex after development of chronic epileptization of the brain (pharmacological kindling)

Experiments on Wistar rats showed that basal and muscimol-induced ³⁶Cl⁻ entry into synaptoneurosomes isolated from the brain cortex decreased after kindling (30 mg/kg pentylenetetrazole intraperitoneally for 30 days) in animals with seizure severity score 4–5. Changes in Cl⁻ conduction during kindling are discussed. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 255–258, March, 2008     

Hypertrophic synapses as a factor of formation of persistent pathological centers in the brain in the late postresuscitation period

Clinical death was modelled on albino rats. Synapses in the molecular layer of the cerebral sensorimotor cortex were investigated 1, 2, 3, 4, 5, 6, 7, 8, and 9 months postresuscitation. The total density of synapses peaked and the number of hypertrophic and perforated contacts increased 4, 7, and 9 months after resuscitation. The role of increased number of hypertrophic and perforated contacts in the pathogenesis of postresuscitation encephalopathy is discussed. Translated fromByuleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129 No. 5, pp. 532–535, May, 2000     

Cold adaptation modulates Ca<Superscript>2+</Superscript> signaling in brown preadipocytes

One-week cold exposure of mice led to a 2-fold increase in the density of α₁-adrenoceptors in brown adipose tissue. The density of α₁-adrenoceptors returned to normal after adaptation to cold for 2 weeks. The reduced Ca²⁺ signaling in stem cells of brown fat activated via β-adrenoceptors and cAMP was transformed into the Ca²⁺-system induced by α₁-adrenoceptors and similar to that in mature brown adipocytes. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 59–62, July, 2004     

Unraveling Changes in Myocardial Contractility During Human Fetal Growth: A Finite Element Analysis Based on <Emphasis Type="Italic">In Vivo</Emphasis> Ultrasound Measurements

Knowledge of normal fetal heart (FH) performance and development is crucial for evaluating and understanding how various congenital heart lesions may modify heart contractility during the gestational period. However, since biomechanical models of FH are still lacking, structural approaches proposed to describe the mechanical behavior of the adult human heart cannot be used to model the evolution of the FH. In this paper, a finite element model of the healthy FH wall is developed to quantify its mechanical properties during the gestational period. An idealized thick-walled ellipsoidal shape was used to model the left ventricle (LV). The diastolic LV geometry was reconstructed from in vivo ultrasound measurements performed on 24 normal FHs between 20 and 37 weeks of gestation. An anisotropic hyperelastic constitutive law describing the mechanical properties of the passive and active myocardium was used. The evolution of the mechanical properties of the normal LV myocardium during fetal growth was obtained by successfully fitting the ejection fraction predicted by the model to in vivo measurements. We found that only the active tension varies significantly during the gestational period, increasing linearly from 20 kPa (at 20 weeks) to 40 kPa (at 37 weeks of gestation). We propose a possible explanation of the increasing force-generating ability of the myocardial tissue during fetal heart development based on a combination of myocyte enlargement, differentiation, and proliferation kinetics.     

Effect of Ca<Superscript>2+</Superscript> gradient on the structure of sarcoplasmic reticulum membranes

The structure of sarcoplasmic reticulum membranes was studied in the presence of modeled transmembrane Ca²⁺ gradient corresponding to the status of Ca²⁺ depot at different stages of the muscle contraction-relaxation cycle in health and disease. Various sites of the membrane were characterized using spectral analysis of tryptophan, pyrene, and merocyanine-540 fluorescence without evaluating specific changes in the molecules of membrane components (Ca²⁺-ATPase, ryanodine receptor, and lipids). The transmembrane Ca²⁺ gradient modulates the protein-lipid interactions and structural characteristics of the membrane. The proposed model can be used for studies of the effects of pharmacologically active substances and endogenous regulators. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 517–521, November, 2007     

Threshold of seizure activity of the brain and higher nervous activity in the postresuscitation period for intracerebral allotransplantation of fetal neocortex tissue

The threshold of seizure activity of the brain, long-term memory, and learning ability are studied in Wistar rats for bilateral transplantation of fetal nervous tissue in area CA1 of the hippocampus. The grafts are performed on the 2nd, 7th, 14th and 30th days after clinical death caused by asphyxia. A neurotransplantation performed on the 2nd day of the postresuscitation period is found to prevent seizure activity, whereas that performed on the 7th–14th days results in a sharp decline or cessation of spontaneous and induced epileptiform convulsive seizures, prolonged preservation of the long-term memory trace, an improvement of learning ability, and a lessening of defensive and phobic behavior in a large proportion of the animals. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 234–237, February, 1996 Presented by V. A. Negovskii, Member of the Russian Academy of Medical Sciences     

Distribution of <Superscript>3</Superscript>H-Dopamine and <Superscript>3</Superscript>H-DAGO Binding Sites in the Central Part of Rat Sinoatrial Node

Distribution of ³H-dopamine and ³H-DAGO binding sites was studied by autoradiography on semithin sections of total preparations of rat sinoatrial node. The relative density of ³H-dopamine and ³H-DAGO binding sites in the functional nucleus of the sinoatrial node was minimum and increased in the cranial and caudal directions. The level of ³H-dopamine binding in the perinodal atrial myocardium was appreciably lower (22±6%), while binding of ³H-DAGO was similar (76±16%) to that in the periarterial zone of the sinoatrial node. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 210–214, August, 2005     

M<Subscript>3</Subscript> cholinergic receptors are involved in postnatal development of cholinergic regulation of cardiac activity in rats

We studied the role of M₃ cholinergic receptors in the regulation of cardiac activity in rats during early postnatal ontogeny in vivo. Blockade of M₃ cholinergic receptors in 20-week-old animals increased heart rate and decreased blood pressure. In rats aging 8, 6, and 3 weeks, blockade of M₃ cholinergic receptors had little effect on R-R interval, but unexpectedly increased it in 1-week-old animals. It can be hypothesized that tonic inhibitory effect of the vagus nerve in adult rats is realized through M₃ cholinergic receptors of the heart. The decrease in heart rate during blockade of M₃ cholinergic receptors in 1-week-old rats was probably related to specific innervation of the heart in animals of this age. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 8, pp. 135–137, August, 2007     

Relationship between H<Superscript>+</Superscript> transfer through human erythrocyte membrane and temperature

The parameters of thermal dependence of H⁺ transport into human erythrocytes in the presence of furosemide were measured. The relationship between these changes and function of band 3 protein of the erythrocyte membrane is discussed. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 54–55, July, 2004     

Left ventricular pressure–volume relationships during normal growth and development in the adult rat – studies in 8‐ and 50‐week‐old male Wistar rats

Aims: Left ventricular (LV) pressure–volume relations provide relatively load‐independent indexes of systolic and diastolic LV function, but few data are available on pressure–volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight‐correction is used as a surrogate for heart weight‐correction. Methods: We determined pressure–volume relations in young (8‐week‐old, n = 13) and middle‐aged (50‐week‐old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure‐conductance catheter was introduced into the LV to measure pressure–volume relations. Results: Heart and body weights were significantly higher in the 50‐week‐old rats, whereas the heart‐to‐body weight ratio was significantly lower (2.74 ± 0.32 vs. 4.41 ± 0.37 mg g^?1, P < 0.001). Intrinsic systolic function, quantified by the slopes of the end‐systolic pressure–volume relation (E_ES), the dP/dt_MAX vs. end‐diastolic volume relation (S‐dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50‐week‐old rats (S‐dP: ?6%, P < 0.004; PRSW: ?3%, P < 0.06). Heart weight‐corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body‐weight corrected pressure–volume indexes showed improved systolic function and significantly depressed diastolic function. Conclusions: Intrinsic systolic function slightly decreases from the juvenile to the middle‐aged period in normal male Wistar rats. Furthermore, correction of pressure–volume indexes for body weight is not an adequate surrogate for heart weight‐correction in these animals.     

Dipeptide γ-d-Glu-d-Trp (thymodepressin) inhibits migration of Cd34<Superscript>+</Superscript> cells from the bone marrow into peripheral blood during tumor growth

We studied the effect of dipeptide γ-d-Glu-d-Trp (thymodepressin) on migration of CD34⁺ hemopoietic precursors and their direct adhesion to fibronectin in tumor-bearing mice on days 8, 11, 15, and 17 of tumor growth and on expression of CXCR-4 (CD184⁺) to SDF-1 and integrin β₁ (CD29⁺) by bone marrow cells. In tumor-bearing mice treated with γ-d-Glu-d-Trp, the percent of CD34⁺ hemopoietic precursors in the peripheral blood considerably decreased throughout the observation period; the content of CD34⁺ hemopoietic precursors in the tumor tissue was 2–3-fold below the control against the background of increased content of CD34⁺ cells in the bone marrow. In animals treated with the peptide, the content of cells expressing CXCR-4 in the peripheral blood, bone marrow, and tumor tissue significantly decreased, while the percent of cells expressing integrin β₁ receptor (CD29⁺) in the bone marrow increased 2-fold, which was paralleled by an almost 2-fold increase in the percent of cells binding to fibronectin. We hypothesized that dipeptide γ-d-Glu-d-Trp suppressed mobilization/migration of CD34⁺ hemopoietic precursor cells from the bone marrow to the peripheral blood of tumor-bearing mice. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 7, pp. 105–108, July, 2008     

Changes in Duodenal Lymphoid Structures in Rats with Different Levels of Behavioral Activity Treated with Delta Sleep-Inducing Peptide and during Acute Emotional Stress

The effects of delta sleep-inducing peptide (DSIP) on intestinal lymphoid formations were studied. Experiments were performed on 42 male Wistar rats which had previously been tested in an open field. The results of this test were used to divide the rats into behaviorally active (predicted to be stress-resistant) and passive (stress-susceptible) animals. Stress was applied by restraining the animals in boxes with electrical stimulation of the back for 1 h. Administration of i.p. DSIP to rats led to decreases in the number of eosinophils in animals of all experimental groups. In active rats of the control group, administration of DSIP produced increases in the numbers of small and intermediate lymphocytes which were greater than increases in passive rats. After acute stress, behaviorally active rats showed increases in the number of lymphoid cells, mainly due to small and intermediate lymphocytes. In passive rats, stress and injection of DSIP were followed by increases in the numbers of plasma cells in all the duodenal mucosal structures studied.     

CD<Subscript>4</Subscript><Superscript>+</Superscript>CD<Subscript>25</Subscript><Superscript>+</Superscript> Regulatory T Cells Decreased the Antitumor Activity of Cytokine-Induced Killer (CIK) Cells of Lung Cancer Patients

CD₄ ⁺CD₂₅ ⁺ regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro. After depletion of CD₄ ⁺CD₂₅ ⁺ cells before culture, the proliferation and cytotoxicity of CIK cells, which indicated in bromodeoxyuridine (BrdU) and lactic dehydrogenase (LDH) assays, were significantly increased. Depletion of CD₄ ⁺CD₂₅ ⁺ cells preculture also enhanced the suppression effect on the lung cancer cells inoculated in experimental animals. Blockage of glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor β1 (TGF-β1) by antibodies partially abrogated the suppressive effect of CD₄ ⁺CD₂₅ ⁺ cells on CIK. These results indicated that Tregs could inhibit the antitumor activity of CIK cells. The molecules TGF-β and GITR may contribute to the suppressive function of CD₄ ⁺CD₂₅ ⁺ cells.     

Intensity of Oxidative and Antioxidant Processes in the Brain of Rats with Various Behavioral Characteristics during Acute Stress

We studied the effect of acute emotional stress (1-h immobilization with simultaneous electrocutaneous stimulation) on the prooxidant-antioxidant balance in emotiogenic structures of the brain in rats with various behavioral characteristics. TBA-reactive substance content in the hypothalamus of rats remained practically unchanged after stress exposure. Opposite change in activity of antioxidant defense enzymes in this structure of the brain in behaviorally active specimens probably compensate for the possible variations in LPO during emotional stress. Activities of glutathione reductase and Cu/Zn-containing SOD in the hypothalamus of passive animals decreased under these conditions. As differentiated from active rats, emotional stress in passive specimens was accompanied by the accumulation of TBA-reactive substances in the sensorimotor cortex and amygdala. The observed increase in glutathione peroxidase activity in passive animals probably serves as a secondary compensatory reaction to LPO activation. Our results illustrate specific changes in free radical processes and antioxidant defense in emotiogenic structures of the brain in rats with various behavioral characteristics after acute stress. These changes were more pronounced in behaviorally passive specimens than in active animals. It was probably related to differences in the oxidative status of CNS in rats with various prognostic resistance to similar stress factors.     

Effect of melatonin on the thymus, adrenal glands, and spleen in rats during acute stress

We studied the effects of acute stress and exogenous melatonin on stress marker organs in rats. Administration of melatonin under normal conditions increased the relative weights of the thymus (active rats) and adrenal glands (active and passive rats). The relative weight of the spleen also tended to increase after melatonin treatment. Stress led to involution of the thymus and hypertrophy of the adrenal glands in active and especially in passive animals receiving physiological saline. Melatonin partially or completely prevented involution of the thymus under stress conditions. Stress had no effect on the relative weight of the adrenal glands in melatonin-treated rats. The relative weight of the spleen in active rats receiving melatonin in doses of 0.5 and 1 mg/kg decreased after stress exposure. Our results suggest that melatonin modulates the hemodynamics and function of stress marker organs. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 3, pp. 263–266, March, 2006     

Psychoemotional manifestations in hippocampectomized rats

The effects of lesioning of the dorsal hippocampus on the psychoemotional state of Wistar rats were studied. Hippocampal lesions did not affect the learning process, but affected mainly the pattern of psychoemotional manifestations in all animals regardless of the typology of higher nervous activity. All animals showed reductions in the extremes of types of passive and active stress reactions. Individual effects depended on the behavioral phenotypes of the animals. Hippocampal lesions in rapidly learning rats (10%) led to sharp decreases in irritability (active/passive = 0.35/0.5 instead of 1.0/0.4), while passive-defensive manifestations were not altered. In slowly learning animals (30%), hippocampal lesions were not accompanied by qualitative changes in the patterns of psychoemotional manifestations, while non-learning rats (60%) showed decreases in passive and increases in active manifestations (active/passive = 0.45/1.4 instead of 0.3/1.9). It is suggested that the hippocampus is involved in producing psychoemotional reactions, individual patterns of which depend on the morphofunctional characteristics of the system responsible for organizing the psychoemotional state.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 7, pp. 868–878, July, 2003.     

Passive avoidance in prenatally X-irradiated rats

Twenty-nine albino rats which had received 200 R of X irradiation on the 16th day of gestation were given together with 38 nonirradiated control animals, 4 trials in a passive avoidance conditioning situation. Irradiated animals showed significantly more passive avoidance behavior than did the controls. In a second experiment, animals from both groups were subsequently tested in a shuttle-box, active avoidance situation. Here, also, the irradiated animals showed more avoidance behavior than the controls. It was hypothesized that the findings are related to increased fearfulness in prenatally irradiated rats.     

Gaba- and Serotonin-Immunoreactive Structures and Ca<Superscript>2+</Superscript>-Binding Protein in the Neocortex of the Reeler Mouse Mutant

The transmitter organization of anomalously formed neocortex was studied in reeler mutant mice by immunohistochemical studies of GABA- and serotoninergic structures and Ca²⁺-binding protein. GABAergic structures were identified in terms of the localization of glutamate decarboxylase (GDC) within them, this being an enzyme involved in GABA synthesis. The neocortex of reeler mutant mice was found to contain an unusual distribution of cells morphologically and chemically identical to Cajal—Retzius cells — beneath layer I rather than in its upper third, as seen in normal animals. GDC-immunoreactive label accumulated in the neuropil of the intermediate and deep layers, layer I containing only occasional granules. Serotonin-immunoreactive fibers did not form superficial or deep plexuses, as seen in normal animals, though they did reach their innervation targets. Thus, the anomalously formed neocortex which lacks the typical cytoarchitectonic organization, showed abnormalities in the structure of both intrinsic and projectional transmitter systems. __________ Translated from Morfologiya, Vol. 126, No. 6, pp. 15–19, November–December, 2004. Director: Corresponding Member of the Russian Academy of Medical Sciences Professor V. A. Otellin     

Active and Passive Behavior of Animals during the Postresuscitation Period

Behavioral reactions (open-field test, elevated plus-maze, pain stress, and feeding behavior) were studied in various periods after clinical death caused by circulatory arrest for 10 or 15 min. We revealed two different phases of behavioral changes: active behavior directed at attaining a specific goal and passive behavior directed towards isolation of the organism from external signals and functional minimization. Active behavior determined by pathological excitation in the central nervous system increased the severity of structural damage to hippocampal CA1 neurons during the postresuscitation period. By contrast, passive behavior and minimization of functions preserved structural integrity in these neurons.