Violation of the main regulatory mechanisms at the level of nerve cells can lead to the phenomenon of neurotoxicity/excitotoxicity of glutamate. Such phenomena most often occur under hypoxia/ischemia, inflammatory processes, and activation of immune and autoimmune reactions. Pathological changes in the brain at the early stages of diseases are nonspecific. They differ little from the physiological norm. Such typical pathological processes are characteristic of numerous diseases. They also develop in ischemic and hemorrhagic strokes. The main task of this work was to analyze some physiological and cytochemical processes that are associated with the neurotransmitter glutamate, as well as with highly reactive and highly toxic compounds, reactive forms of nitrogen and oxygen. The reactive forms of nitrogen ( ^∙NO ) and oxygen ( ^∙O_2^ - ) can affect almost all major components of cells and subcellular structures. At low concentrations, they perform a regulatory function. The analysis of the mechanisms of toxic effects of glutamate, reactive forms of nitrogen and oxygen species as a model of stroke allowed us to propose new ways to protect against the damaging effects of the above substances, which can be used in the treatment of ischemic and hemorrhagic strokes.

The mortality rate increases exponentially with age. The rapid progression of age-related dis-eases is due to the formation of vicious cycles involving reactive forms of nitrogen and oxygen. Such cycles, when the normal regulatory cycles of nitric oxide and superoxide are disrupted, and the toxic products of biochemical reactions initiate a new restart of reactions, involving •NO2, •O2-, peroxynitrites against the background of disrupted regulatory cycles of NO and •O2-

The functioning of the nervous system is based on the process of communication between nerve cells. This process is carried out in specialized areas - synapses. In most synapses, signal transmission occurs through the release of specialized substances from nerve endings - mediators during exocytosis of synaptic vesicles. The molecular mechanisms of synaptic transmission at chemical synapses occupy a central place in neurophysiology. These mechanisms involve the intracellular transport of substances within cells, which is necessary to maintain homeostasis in nerve cells by responding to physiological signals. Proteins synthesized in the cytosol are distributed to the appropriate organelles according to the sorting sequence of their specific amino acids. This short report analyzes the contribution of famous scientists working in the USA to the discovery of the mechanisms of vesicular transport - the main transport system in the cells of living organisms. For these studies, three American scientists - Randy W. Schekman, born in 1948, in the USA; James E. Rothman, born in 1950, in the USA, and Thomas C. Südhof, born in 1955 in Germany, but worked in the USA were awarded the Nobel Prize (2013).

Introduction. Inflammation and activation of the immune system are the main cause of secondary injuries in traumatic brain injury (TBI). Given the central role of nitric oxide (NO) in the neuronal Glu cascade with significant changes in the content of ATP in neurons, as well as the presence of GluRc NMDA-type in lymphocytes, it is relevant to determine the effect of NO on the lymphocytes’ adenosine triphosphate (ATP) content. The aim of the work was to determine the effect of different concentrations of NO-generating compounds (NaNO2 and S-nitrosocysteine) on the content of intra- (hcATP) and extracellular ATP (ecATP) in human lymphocytes and to establish links between NO formed during TBI and the initiation of autoimmune processes in children with TBI of varying severity. Materials and methods. Blood samples from 36 TBI children were used for analysis. Lymphocytes were isolated in a ficol gradient according to a standard procedure. The ATP concentration in the tris-acetate buffer (pH 7.76) was determined on a Lucy-1 luminometer using luciferin luciferase (Promega). The ATP concentration was expressed in nmol/mg of protein, which was determined by the Bradford method using Fluka kits. Results. An increase in the level of ATP in lymphocytes immediately after TBI was found to be a positive factor reflecting the activation of lymphocytes. At the same time, a higher level of autontibodies (aAT) to GluRc immediately after severe TBI is a favourable sign for the TBI outcome and coincides with an increase in CGAP in lymphocytes. Prolonged negative trend in ATP content in lymphocytes with similar changes in serum ATP concentrations in severe TBI is an indicator of an unfavourable outcome of severe TBI in children. Conclusion. A moderate increase in NO in the blood immediately after TBI contributes to an increase in CGAP in lymphocytes and aAT to GluRc, which activates the immune response and protects the brain from hypoxic damage.

Introduction. Inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases with an autoimmune attack on the gastrointestinal tract. Insufficient knowledge of the pathogenesis and the lack of reliable biomarkers of the severity of the condition in IBD dictates the need to search for new prognostic markers to assess the condition and effectiveness of therapy in IBD patients during remission and exacerbation of diseases. The aim of the work was to evaluate the protein profile, the amount of ischemia-modified albumin (IMA) and the content of 3-nitrotyrosine (3-NT) in the blood serum in IBD children. Materials and methods. In the blood serum of twenty two children in accordance with the pediatric indices of PCDAI/PUC disease activity in remission and exacerbation of IBD, electrophoretic separation of serum proteins was performed on the Hydrases 2 scan focusing device (Sebia). The content of IMA was determined by colorimetric method, 3-NT — by enzyme immunoassay (Hycult-Biotech, USA). Results. The article presents data on the content of fractions of albumin (A) and globulins, IMA, and 3-NT in the blood serum in children with different severity of IBD (CD and UC), corresponding to remission and exacerbation of diseases. It was shown that the more severe the condition, the more pronounced the decrease in A with an increase in the fraction of acute phase proteins and a decrease in the albumin/globulin index (A/G). Simultaneously with a decrease in the level of A, the content of IMA and 3-NT indicators of oxidative and nitrosative stress increases. Conclusion. The results obtained indicate modifications of serum proteins and the presence of oxidative and nitrosative stress in children with severe IBD. Due to the fact that such changes are typical for hypoxic brain damage and hyperstimulation of glutamate receptors (GluRc) of neurons, it is suggested that the indicators of oxidative and nitrosative stress in IBD children are associated with the possible development of disorders in the brain through GluRc activation.

— The chaotic advection of a passive admixture during the excitation of chains of vortex structures in circular barotropic flows with a complex two-jet velocity profile simulating mesoscale zonal flows in the ocean, the Earth’s atmosphere, and laboratory experiments is studied studied. Most attention is focused on chaotic advection in the regime of Eulerian dynamical chaos. The description of the generation of structures is based on the numerical solution of the equations of a barotropic (quasi-two-dimensional) flow, taking into account external friction and the beta effect. Zero flow and no-slip conditions are imposed at the walls of the circular channel. The critical values of the parameters at the threshold of instability are found, and the transition to Eulerian chaos in two-jet streams with a complex velocity profile is studied. Basing on a calculation of the finite-time Lyapunov exponent, regions of the circular flow in which the Lagrangian chaos (stochastic mixing) arises are determined. It is shown that, as a result of the expansion of the regions of stochastic mixing during the transition to the Eulerian chaos regime, the propagation of an initially localized passive admixture over the entire volume of the flow is possible. Estimates are given that confirm the possibility of observing the effects in real conditions.

The article discusses the literature data on the relationship of modified albumin by ishemia (IMA) and nitrosative stress (nitroalbumin/nitrotyrosine) to the ischemic/hypoxic damage of the brain and other organs. Data on the association of an increase in the content of IMA with a violation of the binding of serum albumin of metals, which is observed in processes accompanied by oxidative oxygen and nitrosative stress, are presented.

The article discusses the mechanisms of development of a typical pathological process, oxi-dative and nitrosative stress, which underlie many neurological disorders and other known diseases. Cycles of nitric oxide and superoxide anion-radical under physiological conditions do not allow the development of pathological changes in the vital systems of the body. How-ever, when they are damaged, the main regulatory mechanisms are violated, and “dysregula-tory pathology” sets in (G.N. Kryzhanovsky), due to the formation of extremely active com-pounds - nitrogen dioxide (NO2), OH-radicals and peroxynitrites, which, after protonation, decompose again with the formation of radicals NO2 and OH radicals. It is hypothesized that it is these mechanisms that disrupt the cycles of nitric oxide and the superoxide anion radical that underlie the development of a typical pathological process.

The brain and gastrointestinal tract are the most important organs responsible for detecting, transmitting, integrating, and responding to signals coming from the internal and external environment. A bidirectional system of neurohumoral communication (the “intestine–brain” axis) combines the activity of the intestine and brain (or brain and intestine) of a person. It affects human development and behavior. This paper analyzes the literature data on the existence of a relationship between the central and enteral nervous systems. Based on data on the number of neurons in the enteral nervous system (approximately 250 million nerve cells), the concept of a “second brain” in the intestine has been proposed in foreign literature, which, by its influence on the brain, can have a more powerful influence than the spinal cord (approximately 10 million neurons) with its autonomic nervous system. However, it turned out that Russian scientists, academicians of the Academy of Sciences of the Soviet Union I.P. Pavlov, K.M. Bykov, and A.M. Ugolev, analyzed cortical-visceral relationships in the 20th century and wrote about the existence of a connection between the central and enteral nervous systems. One of the urgent problems of modern physiology, pathophysiology, biophysics, biochemistry, and medicine is to clarify the causal relationship between the central and enteral nervous systems, as well as between neurological, mental, and gastrointestinal diseases in order to combine the efforts of specialists of various medical and biological profiles to solve urgent medical problems.

This paper describes the gangliopexy method, a method for creating a new center of local neurohumoral regulation, based on the formation of new connections discovered between the nervous system and the vascular system. The prospects for the development of this method are studied. At the same time, novel concepts about the cycles of nitric oxide and the superoxide anion radical are introduced. A possible role of these cycles is examined in the protection of cells and the body as a whole against oxidative and nitrosative stress, which develops when (in 5-30% of cases) destructive changes in the displaced ganglion lead to vascular complications and an increased risk of mortality. Mechanisms that can protect nerve cells, prevent the development of destructive changes in these cells and reduce the risk of mortality are also investigated.

In children with mild and severe traumatic brain injury (TBI), the role of various damage/repair neuromarkers in the outcomes of trauma was studied. It has been shown that in the first days after TBI with adverse outcomes, there was a significant increase in NSE, S100b, NO products and a decrease in the content of BDNF and autoantibodies to NMDA (NR2) glutamate receptors (Glu) in the blood serum. After 6 months with unfavorable outcomes, there was an increase in aAb to S100b and a decrease in BDNF.

Brain biomarkers (protein S100b and neuron-specific enolase (NSE)), antibodies (aAb) to the NR2 subunit of N-methyl-D-aspartate (NR2(NMDA)) and to the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluR1(AMPA)) subtype of glutamate receptors (GluR), NR2 and AMPA peptides, nitrogen oxides (NOx; "nitrites and nitrates"), and 3-nitrotyrosine (NT) were measured in blood from 159 children after mild traumatic brain injury (mTBI), moderate traumatic brain injury (mdTBI), or severe traumatic brain injury (sTBI) within 1-2 days and at intervals during the first 15 days after brain trauma. S100b and NSE levels on the first day were not a strict criterion for injury outcomes. Children with mTBI had the most significant elevations in antibodies to NR2(NMDA) and AMPA peptides, a slight increase in NOx, and, in 25% of cases, appearance of NT in the blood right after TBI. The lowest level of antibodies to NR2(NMDA) GluR detected shortly after the initial TBI was found in children with sTBI, with a negative outcome. The opposite characters of antibodies to NR2(NMDA) on the first day in children with mild and moderate versus severe TBI may be associated with an important mechanism aimed at protecting neurons from Glu excitotoxicity. We hypothesized that a slight increase in NOx after the onset of TBI rapidly activates the innate immune system and contributes to an increase in antibodies to NR2(NMDA). An increase in the AMPA peptide level in mTBI may be early signs of diffuse axonal injury.

The review presents an analysis and generalization of literature data and the results of our own studies on the mechanisms of action of nitric oxide on blood vessels and the brain under normal physiological conditions, as well as during hypoxia / ischemia.

The article analyzes the Cyclicity Principle, together with the atomic principle of the structure of matter and the holographic principle. According to the developed concepts, the above principles make it possible to answer the question: how nature is unified, and how living organisms ensure the regulation and stabilization of nitric oxide (NO), superoxide anion-radical (•O2-) and hydrogen sulfide/sulfur dioxide (H2S/SO2), involved in intra- and intercellular signaling in mammals. Keywords Atomic Principle of the Structure of Matter; Cyclic Principle; Holographic Principle; Hydrogen Sulfide/Sulfur Dioxide Cycle; Nitric Oxide Cycle; Regulation of the Content of Reactive Nitrogen and Oxygen Species; Superoxide Anion-Radical Cycle

Objective. To compare the genotypes at the apolipoprotein E (APOE) gene with outcomes and level of neural markers in children with severe traumatic brain injury (TBI). Materials and methods. A total of 69 children with severe TBI underwent typing of APOE polymorphisms and estimation of the contents of the following markers of brain damage/repair: neuron-specific enolase (NSE), S100b protein, autoantibodies (aAB) to glutamate receptors (NR2 subunits of glutamate receptors), aAB to S100b, and brain-derived neurotrophic factor (BDNF). Results and conclusions. The study cohort of children with severe TBI showed no link between the characteristics of the APOE 3/3, 3/4, or 3/2 genotypes and outcomes assessed on the Glasgow scale. The largest number of favorable outcomes was seen with the APOE genotype 3/3 (60%). Among children with the other two genotypes – APOE 3/4 and 3/2 – favorable and unfavorable outcomes were distributed 50:50. A significant link with genotype was seen for BDNF: a normal level was seen for APOE 3/3, while the level was reduced for APOE 3/2. Correlational links between neural marker contents and assessments on the Glasgow scale were seen for BDNF and aAB to S100b. BDNF levels were normal and aAB to S100b levels were low for favorable TBI outcomes. All APOE genotypes were combined by the observation that in the longer term, 95% of children with severe TBI showed significant increases in aAB to glutamate receptors and most showed increases in blood aAB to S100b. We link this observation with cerebral hypoxia, activation of autoimmune processes, and increases in the permeability of the blood:brain barrier, which may promote increases in NO content and intensification of oxidative processes in children with severe TBI.

The proposed concept of the cyclic organization of gas transmitters allows us to answer the question: how do living organisms provide regulation and stabilization of these physiologically active compounds involved in intracellular and intercellular signaling.

In children with epilepsy and traumatic brain injury (TBI), the content of autoantibodies (aAb) to glutamate receptors (NMDA and AMPA subtypes) and the level of nitric oxide products - nitrothyrosine (NT) and nitrates/ nitrites (NOx) in the blood were studied. The obtained data make it possible to reveal the specificity of damage to AMPA and NMDA subtypes of glutamate receptors in convulsive states and posttraumatic brain injuries. The participation of NO and its products in the development of autoimmune response was revealed.

In this paper, we are concerned with the transition to dynamical chaos and related anomalous transport of a passive scalar in the annular Kolmogorov flow, which is considered as a model of the barotropic zonal flows in the Earth’s atmosphere and ocean or their laboratory analogs. The investigation of the anomalous transport is conducted within a dynamically consistent flow model describing the saturation of barotropic instability. The analysis is based on the numerical solution of equations of a quasi-two-dimensional flow in an annular channel with rigid walls taking into account the beta-effect and external (bottom) friction. It is supposed that the sinusoidal velocity profile of the Kolmogorov flow has three periods inside a channel and the sticking condition on the channel walls is satisfied. Four basic regimes arising with increasing flow supercriticality, the last of which corresponds to dynamical chaos, are distinguished. It is found that five modulated chains of wave-vortex structures with closed streamlines are formed in the channel and their temporal behavior is studied by making videos. The frequency–wavenumber spectra of the longitudinal velocity at certain values of radial coordinates are drawn and the largest Lyapunov exponent is determined in the regime of dynamical chaos. The relationship between the streamlines behavior and the discrete peaks of frequency–wavenumber spectra is elucidated. The occurrence of anomalous transport of a passive scalar is confirmed by drawing trajectories of tracer particles, as well as by determining exponents of the time dependence of mean particle displacement and its variance.