Effect of early sensory experience on the exploratory activity in adult animals.

It was previously found that the exploratory activity of adult Wistar rats with their vibrissae cut in the period from 9 to 20 postnatal days was characterized by lower intragroup variability in comparison with control rats [3]. The present study has shown that the earlier limitation of species-specific afferentation (whisker trimming on postnatal days 2-9) does not induce such changes. We conclude that high plasticity of the brain during the early postnatal period provides better adaptation to the deficit of sensory information.

[Computer simulation of fibroblast effect on electrical activity in sinoatrial node cells].

Computer simulation of the electrical activity in sinoatrial node cells interacting via gap junctions with fibroblasts revealed that interaction with fibroblasts results in greater oscillation frequency of sinoatrial node cells. We have found out that fibroblasts also decrease the oscillation amplitude of the intrinsic central cells or completely suppress their spontaneous activity, while weakly affect the oscillation amplitude of peripheral cells.

Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system.

Indirect evidence suggests the increased production of reactive oxygen species (ROS) in migraine pathophysiology. In the current study we measured lipid peroxidation product in the rat cortex, trigeminal ganglia and meninges after the induction of cortical spreading depression (CSD), a phenomenon known to be associated with migraine aura, and tested nociceptive firing triggered by ROS in trigeminal nerves ex vivo. Application of KCl to dura mater in anesthetized rats induced several waves of CSD recorded by an extracellular electrode in the cortex. Following CSD, samples of cortex (affected regions were identified with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI)), meninges from left and right hemispheres and trigeminal ganglia were taken for biochemical analysis. We found that CSD increased the level of the lipid peroxidation product malondialdehyde (MDA) in the ipsilateral cerebral cortex and meninges, but also in both ipsi- and contralateral trigeminal ganglia. In order to test the pro-nociceptive action of ROS, we applied the mild oxidant hydrogen peroxide to isolated rat hemiskull preparations including preserved trigeminal innervations. Application of hydrogen peroxide to meninges transiently enhanced electrical spiking activity of trigeminal nerves showing a pro-nociceptive action of ROS. In the presence of hydrogen peroxide trigeminal nerves still responded to capsaicin by burst of spiking activity indicating integrity of neuronal structures. The action of hydrogen peroxide was mediated by TRPA1 receptors as it was abolished by the specific TRPA1 antagonist TCS-5861528. Using dorsal root ganglion sensory neurons as test system we found that hydrogen peroxide promoted the release of the migraine mediator calcitonin gene-related peptide (CGRP), which we previously identified as a trigger of delayed sensitization of trigeminal neurons. Our data suggest that, after CSD, oxidative stress spreads downstream within the trigeminal nociceptive system and could be involved in the coupling of CSD with the activation of trigeminovascular system in migraine pathology.

[Computer simulations of microreentry in the SAN].

We have studied the dynamics of reentry inside the SAN. We have found that reentry is unstable at high intercellular conductance. Rotating reentry induces a slow migrating crescent-shaped functional block near the boundary of the SAN. An abnormal conduction from atrial tissue into the SAN occurs after decay of the reentry. ACh increases lifespan of the reentry in the SAN.

[Stroke incidence and mortality in the North Easten region of Azerbaijan Republic].

The research objective consisted in studying 10-year (1999-2008) dynamics of incidence and mortality rate of stroke in the northeast region of Azerbaijan. All cases of stroke in the region have been retrospectively studied. The 10-year chronological average level of incidence of stroke was 1.2±0.05‰, the mortality rate from a stroke was 0.4±0.03‰. Among all strokes, 67.5±0.6% was ischemic stroke, 18.3±0.5% was hemorrhagic stroke and 5.3±0.3% subarachnoid hemorrhage. It was not possible to specify the type of stroke in 9.0±0.4% of cases. A trend towards lower incidence of a stroke in the region in 1999-2008 was noted. Survival after the stroke has averaged 2.08 years and didn't change significantly in 1999-2008. On average, 1/3 patients with stroke die within a year. The indicator of annual mortality in 1999-2008 showed no statistically significant changes, with interval 31.5±1.7-37.2±2.2%.

[Coherence and phase analysis of theta-oscillations in the septohippocampal system during seizures].

Interrelations of the hippocampus and medial septal area (MSA) in the theta band (4-8 Hz) were studied during seizures produced by electrical kindling in waking guinea pigs. Field activity (EEG) was analyzed using the wavelet transform. A decrease in coherence of theta-oscillations in the hippocampus and MSA was observed during seizures. Phase analysis showed that in the beginning of kindling the MSA led in phase, but after formation of the pathological focus, MSA lagged the hippocampus. The data may contribute to understanding mechanisms of temporal lobe epilepsy.

[Computer simulations of electrical activity of the heart].

Computer simulations of electrical activity in the heart involve three levels of complexity: simulations of a single cardiocyte, a slab of tissue and the whole organ. For each of the levels there are both conceptual mathematical models to describe the common features of the dynamics, and detailed models to estimate parameters with the precision comparable to that obtained in the experiment. I consider modern approaches and provide examples of simulations; the accent is on simulations of action potential and membrane currents.

[Computer simulations of the preautomatic pause in pacemaker cells of the sinoatrial node].

The duration of the preautomatic pause as a function of sinoatrial node, the type of pacemaker cells, acetylcholine concentration, the duration of high-frequency stimulation, and the conductivity of gap junctions has been studied. It was found that the preautomatic pause in peripheral pacemakers occurs at a higher concentration of acetylcholine as compared with central pacemakers. The dependence of the duration of the preautomatic pause on the gap junction conductivity is a nonlinear one.

[Computer simulations of pacemaker shift in the sinoatrial node].

The initiation and propagation of electrical pulses in the sinoatrial node under normal conditions and after the application of acetylcholine have been simulated. It has been found that normally a single or a few leading centers are formed in the tissue. When acetylcholine is applied, a temporary functional block of conduction may appear; the leading center migrates under these conditions.

[Computer simulations of the effect of gap junctions on the synchronization of central and peripheral sinoatrial node cells].

The electrical activity of couples of central and peripheral sinoatrial node cells interacting via gap junctions has been simulated. It was found that, as the intercellular conductivity decreases, the phase lag increases; a decrease in conductivity below the critical leads to asynchronous oscillations. The magnitude of the phase lag depends upon the type of interacting cells and is maximum for central and peripheral couples of sinoatrial node cells.

[Theoretical and experimental study of the sinoatrial node pacemaker cell response modality in vagal stimulation].

We studied electrical activity of the SAN pacemaker cells under the influence of ACh released after stimulations of the vagus nerves, by means of mathematical modeling and experimental research. We show the reaction of the pacemaker cells being affected by both the phase and the duration of stimulation. We plotted curves of phase sensitivity of pacemakers to vagal stimulation. The paradoxal positive chronotropic effect occurred during a short vagal stimulation.

[Computer simulation of the sinoatrial node pacemaker synchronization in response to periodic stimulation of the vagus nerve].

The effect of periodic stimulation of the vagus nerve on the activity of the central cell of the sinoatrial node has been simulated. The regions of synchronization and desynchronization have been revealed, and the phase shift at different stimulation frequencies has been estimated. The positive chronotropic effect has been shown to occur at some frequencies of stimulation.

[Experimental and theoretical analysis of the role of cholinergically induced local non-excitability in atrial fibrillation and flutter].

Excitation of vagal nerves results in the emergence of temporarily inexcitable regions in atria. The fact is shown using microelectrode techniques and the mapping of excitation on frog atria isolated together with vago-sympathetic trunks. These regions serve as unidirectional block and functional obstacle provoking reentry-type arrhythmia. The mechanism is defined in terms of a two-dimensional mathematical model which elements were axiomatically set to have the following states: rest, excitation, refractoriness, and vagal inexcitability. With the help of the model we have explained the mechanism of initiation, development and termination of neurogenic tachyarrhythmia. Using micro electrode techniques on an isolated rabbit right atrium we have shown that during intramural nerve excitation as well as in the presence of Ach, there occur inexcitable loci within sinoatrial node (SAN). Probability of development of inexcitability negatively correlates with the velocity of AP upstroke of SAN cells. At maximum upstroke rates higher than 3 V/s, 80 to 90% trials of cholinergic interference resulted in inexcitability. At upstroke rates higher than 12 V/s, inexcitability was not observed. Unlike in amphibians, cholinergically induced inexcitability was not observed in rabbit and canine atria. Cholinergically induced inexcitability in central SAN cells has been simulated with the help of a computer model. The model provides a detailed description of transmembrane current and intracellular ion flows. The computed data are in good agreement with available experimental results.

[The effect of fluctuations of the electric potential on the activity of SAN cells].

The effect of fluctuations of the transmembrane potential on the generation of the action potential has been studied using a computer model of a SAN cell. It was shown that the magnitude of the effect increases with increasing concentration of acetylcholine. The effect is well seen near and after the cessation of spontaneous oscillations. While applying and washing acetylcholine, a hysteresis loop has been observed.

[Theoretical analysis of the sinus node pacemaker responses modes depending on temporal characteristics of acetylcholine effect upon them].

We have simulated electrical and vagal stimulation of a central sino-atrial node cell. Both positive and negative chronotropic effects have been observed. The type of the effect is dependent on the phase of stimulation. Stimulation in early phases resulted in shortening of the cycle, while stimulation in late phases resulted in prolongation of the cycle.

[Pattern of excitation in isolated heart of hibernator ground squirrel Citellus undulatus].

Aim of our study was to measure conduction velocity and pattern of excitation during hypothermia in hearts of ground squirrels Citellus undulatus, known to be most resilient hibernators. We imaged electrical conduction in intact isolated hearts of summer active and winter hibernating ground squirrels at temperatures varying from +37 degrees C to +3 degrees C. Electrical activity was mapped using CCD camera (500 frames/sec) and voltage-sensitive dye di-4-ANEPPS during normal sinus rhythm and ventricular pacing. No spontaneous tachyarrhythmia was observed in all hearts at any temperature. Hearts were able to maintain spontaneous sinus rhythm and normal pattern of epicardial excitation throughout the whole range of studied temperatures. Despite responsiveness to pacing in all hearts ventricular conduction velocity was significantly reduced (about 10-fold) at low temperatures +3 degrees C. Our data provides the first direct demonstration that isolated heart of the summer active and winter hibernating ground squirrel Citellus undulatus is able to maintain normal excitation pattern in a range of temperatures from +37 degrees C to +3 degrees C.