Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection.

The aims of the present work were to perform a comparative study of the effects of delta sleep-inducing peptide and Deltaran on neurons in emotiogenic brain structures and to address the question of whether it is possible to prevent or decrease the negative influences of stress loads on the severity of subsequent cerebral ischemia in rats, using glycine with delta sleep-inducing peptide combined in the neuroprotective formulation Deltaran. The results showed that Deltaran and delta sleep-inducing peptide had largely the same actions on the nature of spike activity of neurons in the dorsal hippocampus, paraventricular nucleus of the hypothalamus, and ventral anterior nuclei of the thalamus, evoking activation of some of the neurons in these brain structures. The dorsal hippocampus was dominated by activation of spike activity in response to administration of delta sleep-inducing peptide; Deltaran produced activation mainly in the paraventricular nuclei of the hypothalamus. In all animals given Deltaran, the index of brain blood supply was significantly greater than in animals not given Deltaran. The survival rate of cerebral ischemia was 100% in animals given Deltaran. Death occurred in 38% of animals not given Deltaran.

[Cell-free plasmic DNA as a blood factor determining hemodynamics in health and in vascular pathology].

The article reviews investigations performed in the Research Neurology Institute on blood flow biomechanics which resulted in discovery of a universal permanent theological blood factor--circulating cell-free plasmic DNA reducing hydrodynamic blood resistance in accordance with Toms' effect. In vitro and in vivo experiments were made with use of drag-reducing polymers for correction of circulation. Basic mechanisms were discovered by which cell-free DNA regulates normal and affected circulation. Clinico-experimental investigations demonstrated the role of imbalance between DNA concentration in blood plasma and length of its fragments caused by their change in cerebrovascular diseases, in disorder of circulation pattern. It was shown in animal experiments that it is possible to correct abnormal circulation characteristics in ischemic disorders of brain circulation by intravenous injections of high-molecular DNA solutions.

[A role of the adhesive properties of leucocytes and blood serum in the pathogenesis of multiple sclerosis].

Adhesive properties of leucocytes were studied using an original technique based on the leukocyte adherence inhibition reaction and measuring the values of spontaneous adhesion index (SAI) and adhesion-strengthening effect (ASE) under the influence of autoserum. One hundred patients with multiple sclerosis (MS) and 53 controls were included in the study. Immunophenotyping of lymphocytes (LP) with monoclonal antibodies--markers CD3, CD4, CD8, CD16, CD20, CD25, HLA-DR and CD95--and determination of IgG, IgA, IgM and content of immune complexes were carried out in parallel. The increase of adhesion parameters (ASE and SAI) was found in MS. It was most significant in patients with primary progressive course and in disease exacerbation. The greatest changes of phenotypic LP content were associated with debut and exacerbation-remission periods. Significant positive correlations between higher SAI values and phenotypes CD20, CD95, HLA-DR and amount of natural killer cells were revealed in patients with MS in contrast to the negative correlations of SAI with CD3 and CD4 in the control group. A role of membrane and soluble forms of adhesion molecules in the initiation and progression of immunopathological process in MS is discussed.

[Delta-sleep inducing peptide and the drug deltaran: possible approaches to antistress protection].

An aim of the present study was a comparative investigation of a delta-sleep inducing peptide and the drug deltaran on the neural activity of the brain structures involved in emotional processing. Another goal was to analyze the possibility to prevent negative effects of emotional stress on brain ischemia using, along with deltaran, glycine and a delta-sleep inducing peptide. Deltaran and the delta-sleep inducing peptide exert in general similar effect on the burst activity of neurons in the dorsal hippocampus, hypothalamic paraventricular nucleus and ventral anterior thalamic nucleus, inducing amplification of the majority of recorded units. The activation of neuronal activity was seen mostly after the delta-sleep inducing peptide microiontophoresis in the dorsal hippocampus and after the deltaran application in the hypothalamic paraventricular nuclei. The index characterizing blood supply was significantly higher in all rats receiving deltaran as compared to the controls. Animals receiving deltaran survived experimental brain ischemia in 100% cases versus 38% in those not exposed to this drug.

Effect of emotional stress on hemoglobin oxygen affinity in low resistant animals under normal conditions and during cerebral ischemia.

Hemoglobin oxygen affinity within the estimated physiological range plays an adaptive antioxidant role during acute cerebral ischemia. This range depends on individual emotional resistance. Brain ischemia induced by common carotid artery occlusion in low resistant Wistar rats increased hemoglobin oxygen affinity by 12% during the acute period. Emotional stress also increased hemoglobin oxygen affinity and determined shifts in this parameter during the development of cerebral ischemia: moderate increase in hemoglobin oxygen affinity (<25%) was followed by further increase in this parameter, while more pronounced shift (>25%) resulted in a significant drop in this parameter due to hemoglobin deoxygenation. Adaptation to stress shifted the upper physiological limit for self-regulation of this process.

Deltaran prevents an adverse effect of emotional stress on the course of cerebral ischemia in low-resistant animals.

Local cerebral blood flow in the left hemisphere decreased most significantly in low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively increased blood flow in the left hemisphere and improved blood supply to neuronal activity unit of the brain in these animals. This drug prevented progressive decrease in local cerebral blood flow in both hemispheres during the acute stage of ischemia. The effect of Deltaran was related to modulation of collateral blood flow and adequate blood supply to neuronal activity unit in the brain tissue. Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of cerebral ischemia. The positive effect of Deltaran was more pronounced in the left hemisphere.

[Clinical significance of adhesive properties of leukocytes and blood serum in patients with multiple sclerosis].

Adhesive blood properties have been studied in 100 MS patients with the help of the new method developed on the basis of the leucocyte adherence inhibition (LAI) test, which was based on the calculation of the ratio of adhesive cells to non-adhesive ones. The value obtained was called the Index of Spontaneous Adhesion (ISA), while the respective indicator reflecting the effect of adhesion strengthening under the influence of autoserum, being expressed by 30% and more, was named the Effect of the Adhesion Strengthening (ES-a). Blood samples of 54 donors and 31 patients with other neurological diseases were used as controls. Statistically significant increase of ISA values of MS patients was detected as compared to the group of donors. The highest indices of ISA and ES-a were found in the primarily progressive course and at the stage of MS exacerbation in the remitting course. Correlation between levels of adhesion and clinical features as well as parameters of clinical and humoral immunity are described. A role of membrane and soluble forms of adhesion molecules in initiation and progression of the immunologic process in MS is discussed.

Correction of cerebral ischemia in low-resistant animals with an antistress drug Deltaran.

Deltaran decreased the amplitude of EEG slow waves and restored neuronal reactivity after carotid artery occlusion in Wistar rats sensitive to cerebral ischemia. Deltaran had no effect on local cerebral blood flow. This drug increased blood supply to a unit of neuronal activity in the brain of intact animals during the acute stage of cerebral ischemia, provided 100% survival rate of rats with cerebral ischemia, and prevented the development of neurological symptoms in survivors. Animal experiments proved the possibility of correcting cerebral ischemia with antistress drug Deltaran.

[Long-fragment DNA of blood plasma as one of the criteria of individual sensitivity to emotional stress and to cerebral ischemia].

Intravenous injection ofpolyethylenoxide WSR-301 reducing hydrodynamic blood resistance (Toms effect) improves gas exchange in the lungs and halved lethality of the animals with cerebral ischemia. The aim of the study was to establish whether free plasma DNA influences blood gases and lethality of the animals with brain ischemia. Common carotid arteries were ligated for 15 min in intact stressed and tested in the open field Wistar male rats, then some of the rats received intravenous solution of homologous long-fragment DNA (20x10(-6) g/ml of blood). Cerebral circulation, acid-base equilibrium, paO2, paCO2, asymptotic blood viscosity, plasmic concentration and length of DNA fragments in plasma, lethality and neurological status of the survivors were studied. It was found that long fragments of rat DNA show hydrodynamic Toms effect. In normal passive rats sensitive to cerebral ischemia part of plasm DNA is fragmented, gas composition and blood viscosity of blood is worse (p < 0.05) than in active animals. There is a direct correlation between the level of long-fragment DNA in plasm and paO2 (r = 0.55) and inverse--with paCO2 (r = -0.84). Intravenous injection of long-fragment DNA improved the course and reduced lethality of brain ischemia 2-3-fold. Thus, qualitative and quantitative characteristics of plasma circulating DNA are responsible for differences in blood gases in rats differently tolerable to cerebral ischemia and can serve as one of the criteria of individual sensitivity to it being essential in pathogenesis of ischemic stroke.

Individual resistance to cerebral ischemia and negative effect of emotional stress on the course of this disorder.

The ratio of low-activity and high-activity rats differed in autumn, winter, and spring litters. Initially more intensive cerebral blood flow in low-active rats and its more pronounced decrease after common carotid artery occlusion determined their higher sensitivity to cerebral ischemia (compared to high-activity animals). After 18-h immobilization stress cerebral blood flow decreased by 10-15%, which abolished the difference in the individual resistance to cerebral ischemia. Independently on emotional resistance, cerebral ischemia was not accompanied by the development of collateral blood flow in the acute period and caused death of 90% rats.

[Biochemical and immunological induces of the blood in Parkinson's disease and their correction with the help of laser therapy]. / Biokhimicheskie i immunologicheskie pokazateli krovi pri bolezni Parkinsona i vozmozhnosti ikh korrektsii s pomoshch''iu lazernoi terapii.

The influence of laser therapy on the course of Parkinson's disease (PD) was studied in 70 patients. This influence appeared adaptogenic both in the group with elevated and low MAO B and Cu/Zn SOD activity. Laser therapy resulted in reduction of neurological deficit, normalization of the activity of MAO B, Cu/Zn-SOD and immune indices. There was a correlation between humoral immunity and activity of the antioxidant enzymes (SOD, catalase). This justifies pathogenetically the use of laser therapy in PD.

[Cerebral circulation in different types of brain hypoxia]. / Mozgovoe krovoobrashchenie pri razlichnykh vidakh tsirkuliatornoi gipoksii mozga.

The paper describes differences of hypoxic and circulatory hypoxias (i.e. brain ischemia) which cause decreases not only in the supply of O2, but in the delivery of glucose and other oxidation substrates and in venous return, which is attended by the accumulation of metabolic products in the brain tissue. It also considers the mechanisms of primary and secondary brain ischemia occurring with decreased cerebral circulation due to breakdown of cerebral blood flow autoregulation at its lower and upper borders to develop cytotoxic or vasogeneous brain tissue edema with possible compression of the microcirculatory bed in the latter case. Emphasis is laid on the significance of autoimmune reactions occurring with the impaired blood-brain barrier due to different types of cerebral circulatory disorders, which gives an insight into the cause of progressive damage to the brain in some cases despite its single damage. The paper outlines current therapies for brain ischemia, including those that exert effects on metabolic disturbances and neurosurgical reparative operations. In conclusion, the paper considers a new nontraditional way of increasing collateral CBF by decreasing blood flow pseudoturbulence with special high molecular-weight linear polymer solutions by the Thoms-effect method (1948). The prospects for using this approach in patients with brain ischemia are substantiated by a number of the established facts: 1) the above patients have higher hemodynamic blood flow resistance which may be corrected by adding a polymer solution into the sample in in vitro tests; 2) there was an inverse relationship of the intrinsic plasma concentrations of high molecular-weight fragments of DNA and hemodynamic resistance to the changes in plasma DNA properties in stroke patients.

[The role of serum 'adhesive factor' and leukocyte sensitization in pathogenesis of multiple sclerosis]. / Znachenie "adgezivnogo faktora" syvorotki i sensibilizatsii leikotsitov krovi v patogeneze rasseiannogo skleroza.

The reactivity to the myelin basic protein, brain gangliosides purified derivative and also the influence of the serum on the cells adherence were determined by micromodification of the leukocyte adherence inhibition (LAI) test. 46 multiple sclerosis patients, 21 patients with hereditary disease and 41 donors were examined. The cellular sensitization to the myelin basic protein and brain gangliosides was revealed in 57% of the multiple sclerosis patients. The leukocyte adherence was increase in 53.5% patients when autologous serum was added. The adherence factor was most often found (90% case) in patients with severe neurological deficit. It is suggested that this factor is a connected t the increased levels of circulating adhesion molecules in multiple sclerosis patients.

[Hydrodynamic efficiency of various forms of free DNA]. / Gidrodinamicheskaia éffektivnost' raznykh form svobodnoi DNK.

DNA of blood plasma is the factor which corrects hydrodynamic resistance (HR) of blood flow and provides Thomes' effect. As comparative hydrodynamic effectiveness of various plasma DNA forms (nucleoprotein, thread and denaturated DNA isolated standardly from human leukocytes) remains unknown, the in vitro test identified HR of the flow of the above DNA forms weak solutions--10(-6) to 10(-5) g/ml--necessary for achievement of Thomes' effect in strictly similar hydrodynamic conditions warranting a turbulent flow (Re 8000). Thomes' effect was confirmed in blood samples in its absence in low-molecular solutions (glycerine) with the same asymptotic viscosity. It was found that HR of the flow of synthetic polymer solutions producing Thomes' effect depends on its initial concentrations. Hydrodynamic effectiveness in the used solutions of the nucleoprotein and DNA was high being comparable to that of the synthetic polymer widely used in production for obtaining Thomes' effect.

[Effect of decreasing hydrodynamic resistance of a polymer on localization of sclerotic plaques. A model study]. / Vliianie snizhaiushchego gidrodinamicheskoe soprotivlenie polimera na lokalizatsiiu skleroticheskikh bliashek. Model'noe issledovanie.

Flow structure and wall shear stress and the changes in these parameters induced by the administration of a drag-reducing polymer polyethylene oxide WSR-301 at a concentration of 10(-5) g/ml were studied in a glass tube with a T-junction by the laser Doppler anemometry technique. The pattern of wall shear stresses is in a good agreement with the data, obtained for rabbits in [1]. For tubes with rigid walls, the location of plaques corresponds to regions of a high wall shear stress.

Lipid peroxidation in experimental ischemia of the brain.

Lipid peroxidation was studied in the brain of Mongolian gerbils under conditions of complete ischemia followed by recirculation in the left hemisphere without recirculation in the right hemisphere. Thiobarbituric acid reactive products and the intensity of Fe2+-induced chemiluminescence were determined. The content of lipid peroxidation products in the brain tissue was increased not only under conditions of recirculation, but also at the ischemia stage during the limited access of oxygen. Thus, the destructive effect of free radicals may occur even during the early stage of ischemic injury of the brain.

[Hemodynamic effect of plasma DNA]. / Gemodinamicheskii éffekt DNK plazmy krovi.

To reveal the hemodynamic effect of plasma DNA, the authors measured the concentrations of plasma DNA, the length of its molecular fragments, and hemodynamic resistance/Toms effect. The Toms effect was detected in all blood samples from 10 healthy donors and 39 patients without acute stroke caused by atherosclerosis of the head great arteries with and without arterial hypertension. There was a clear inverse relationships between the plasma concentrations of DNA which had only long-molecular fragments in healthy persons and the hemodynamic resistance of its blood flow samples. The patient blood plasma had significant increased DNA concentrations but their molecular fragments were long and short. Inverse relationships between the plasma DNA concentration and the hemodynamic resistance of the patients' blood flow samples had a less correlation coefficient due to the high proportion of short DNA molecular fragments. The Toms effect was shown in the DNA solution prepared only from human funic blood where the DNA molecular fragments were long. The Toms effect was absent in the solutions prepared from the commercial cattle or salmon sperm DNA which contained shorter DNA molecular fragments. It is concluded that plasma DNA has a hemodynamic effect and the origin of long-molecular fragments of DNA which is typical for healthy young persons and short DNA molecular fragments that additionally appear in patients with vascular disorders is different.

[Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with varying behavioral reactions in the open field test]. / Vliianie nootropa--tserebrolizina pri ishemii mozga u krys s raznymi povedencheskimi reaktsiiami v teste otkrytogo polia.

Open field tests were made on 489 white male rats to distinguish subgroups by baseline higher nervous activity (HNA) to study the effects of cerebrolysin (EBEVE, Austria) on relationships between neuronal activity and cerebral blood supply in normal cerebral circulation (CC) and in acute brain ischemia. Local CC and EEG were measured by laser doppler flowmeter and read from the same point gauge. CC/EEG index was calculated. Cerebrolysin was injected i.p. in a dose 0.3 ml/100 g body mass. Brain ischemia was provoked by occlusion of the common carotid arteries. Neurological symptoms were estimated according to the McGrow scale. Also, 24-h lethality was registered. It was confirmed that cerebrolysin, as an active nootrop, enhances EEG. This effect takes place both in intact and brain ischemia rats. It was also found that cerebrolysin has different effectiveness dependent on the animal's behavior in the open field test, that blood supply to the brain does not increase in cerebrolysin-activated HNA. In stable circulation, this was compensated due to cerebral metabolic reserve, but in intensive EEG activation, recorded by CC/EEG index, cerebrolysin reduces cerebral blood supply aggravating acute brain ischemia.