[The possible role of nitrogen dioxide produced in the field of bifurcation of vessels, in the processes of their damage in hemorrhagic strokes, and the formation of atherosclerotic plaques].

According to modern views the formation of atherosclerotic plaques is associated with accumulation of cholesterol in the vascular wall. This is due to an imbalance between the intake of cholesterol in the intima of vessels, together with the low-density lipoproteins (LDL) and its output with high-density lipoprotein (HDL). Change of LDL (glycosylation, lipid peroxidation, hydrolysis of phospholipids) and the effective release of cholesterol from the endothelium of the vascular wall are the factors that cause an imbalance in cholesterol metabolism. In this paper we propose a new concept of the mechanism of initial formation of atherosclerotic plaques, which can complement the existing concepts. According to this concept an important role in the early stages of atherosclerosis are highly reactive molecules of nitrogen dioxide (NO2), resulting from the violation of the cycles of nitric oxide and superoxide anion radical. Hypothesized that the mechanism of antiradical protection of cells and the organism as a whole, above all, laid out in most of the cyclic organization of metabolic processes that involve the formation of free radicals. Violation of this cyclic mechanism may be one of the causes of many diseases associated with hypoxia/ischemia and inflammation. The review considers the hypothesis of the possibility of participation of NO2 and OH-radicals formed in violation of the cycles of NO and superoxide, in the mechanisms of vascular damage with hemorrhagic stroke and in the formation of atherosclerotic plaques.

[Development of the theory of cardiac innervation during ontogenesis in health and disease].

The paper describes the mediatory stage of prenatal development of cardiac innervation and the phenomenon of early involution of sympathetic nerve plexuses in postnatality, which has been established while analyzing early autopsies by neurohistochemical studies. lmmunocytochemical, luminescence, and ultrastructural techniques have defined changes in the stages of their formation and development of the above early involution. Complex (neurohistochemical and electrophysiological) studies quantified groups of age-related cardiac innervation changes in health. Cardiac rhythm variability was electrophysiologically studied in 43 subjects aged 18-71 years. Cardiac desympathization is shown to develop after 40 years of age. Age-related changes in cardiac regulatory mechanisms should be taken into account on studying visceral systems in coronary heart disease, atherosclerosis, and sudden cardiac death, and during cardiac transplantation. Immunohistochemical study has revealed an increase in nitric oxide expression in the human cardiac nervous apparatus.

[Mast cells and innervation of the wall of the hyperactive urinary bladder].

Anterior urinary bladder wall biopsy specimens were examined in 24 males and 4 females, aged 52 to 76 years, who had been suffering from the hyperactive urinary bladder for 1-10 years. Increases in the number and activity of interstitial mast cells and their degranulation and the symptoms of chronic immune inflammation were revealed. Neuromuscular spastic dysfunction of the detrusor is considered to result from the activation of mast cells.

[Age related changes of regulatory mechanisms of cardio-vascular system and significance of nitric oxide synthase in the norm and pathology].

The article sums up results of thirty-year period of studies of ontogenesis of autonomic nervous system conducted in laboratory of neuromorphology and electron microscopy. It contains discussion of pre- and postnatal ontogenesis of cardiovascular innervation and content of NO-synthase in cardiac ganglia at normal and pathological states. The studies included analysis of 12 series of human germs, examination of cardiovascular system of 23 human fetuses, and of material of 124 early autopsies of persons of different age who died suddenly or of some cardiac diseases. Methods of investigation included neurohistological, histochemical, and ultrastructural techniques; NO-synthase content was measured immunohistochemically. Data of time-frequency spectral analysis of heart rate variability of 43 subjects of different age ("normals" and with ischemic heart disease) are also presented. Conception of the neurotransmitter stage of ontogenesis of autonomic nervous system is formulated, and the phenomenon of early involution of its sympathetic part is described. Neurohistochemical data are compared with results of analysis of heart rate variability at normal and hypertensive states. The original data on nitric oxide synthase content in cardiac ganglia at normal state and coronary heart disease are provided. Prospects of immunohistochemical studies of central and autonomic nervous systems during ontogeny and at main cardiovascular diseases are outlined.

[Nitric oxide synthase in human intracardiac ganglia in the normal and ischemic myocardium].

Nitric oxide synthase (NOS) expression in human intracardiac ganglia was studied using two techniques--histochemical demonstration of NADPH-diaphorase and immunohistochemical staining for NOS. To detect the influence of coronary heart disease on NOS expression, hearts were studied in patients that died from heart failure (n = 8) and in persons that died in accidents (n = 3, control). It was found that human intracardiac neurons normally expressed mainly NOS1, and the proportion of these cells amounted to about 40%. A portion of neurons with low and moderate density of staining for NADPH-diaphorase was increased in ischemic myocardium, probably, due NOS2 induction.

[Distribution of nitric oxide synthase in human intracardiac ganglia].

This is the first study to report presence of nitric oxide synthase (NOS) in the human intracardiac nervous cells. By applying immunohistochemical technique it was shown that majority of neuronal perikaryons contain NOS 1 (neuronal NOS). We conclude that in human heart about half of neurons have NO-ergic phenotype. These cells are also cholinergic and related to parasympathetic part of autonomic nervous system. Moreover in human heart NOS contains pericellular baskets that surround intramural neurons. This points to the presence of the enzyme in parasympathetic preganglionic fibers. A substantial differences of patterns of NOS expression in cardiac neural ganglia between humans and experimental animals are discussed.

[Consequences of the saphenous artery denervation under normal and chronically lowered blood pressure in rats].

We studied constrictor responses of saphenous artery after sympathetic denervation in normotensive rats and rats with chronic regional hypotension. Abdominal aorta was partially occluded in Wistar rats distally to the renal arteries, lowering blood pressure in the hindquarters by about 40%, a week later to denervate saphenous artery the femoral nerve was cut. The density of periarterial nerve plexus and neurogenic responses of the vessel restored partially in 2 weeks and completely in 6 weeks after the surgery; the chronic hypotension did not modify the dynamics of reinnervation. Arteries of both groups of rats demonstrated higher sensitivity to noradrenaline during 6 weeks after denervation, whereas vessel sensitivity to serotonin was enhanced only in normotensive rats. Therefore, chronic hypotension may prevent postdenervation hypersensitivity of vascular smooth muscle to vasoconstrictors.

[Neurotransmitter stage in the development of peripheral part of autonomic nervous system]. / Mediatornyi étap v razvitii perifericheskogo otdela vegetativnoi nervnoi sistemy

The dynamics of neurotransmitter stage in the development of autonomic nervous system (ANS) was studied in rats starting from the moment of initial appearance of neurotransmitters acetylcholine and adrenalin in ANS peripheral part main nervous plexuses. Cryostat sections of embryos on developmental days 13.5, 16.5 and 18.5 and of neonatal rats aged 0.5 and 1.5 days were treated with glyoxilic acid, using Karnovsky-Roots method and impregnated with silver nitrate according to Bielschowsky-Gross method. Acetylcholinesterase in vagus and in spinal ganglia was found on day 13.5, while catecholamine in sympathetic trunc was detected in animals immediately after the birth. Periods of the beginning of neurotransmitter stage in ANS development in rat and man were compared and it was established that it was delayed in rat as in immature-born animal.

[Morphological and morphometrical changes in nervous apparatus of the adrenal medulla after sudden death of patients with various cardiac pathology]. / Morfologicheskie i morfometricheskie izmeneniia nervnogo apparata mozgovogo veshchestva nadpochechnikov pri vnezapnoi smerti u liudei s raznoi serdechnoi patologiei.

Adrenal glands were studied at early autopsy of 28 men aged 35-60 years after their sudden cardiac death. According to the presence and character of pathologic manifestations detected in myocardium, three groups of cases were distinguished: group 1 (control) included the people without myocardial pathology (traffic accident victims), group 2 consisted of the patients with ischemic heart disease (IHD) in association with recent myocardial infarction, group 3 included the patients with IHD and hypertension. The study was performed using the methods of silver impregnation of nerve terminals and planimetric point-counting method. Analysis of density of distribution of nerve plexuses in adrenal medulla in the groups studied has shown a tendency towards its reduction in group 2 and a significant decrease in group 3. Reactive-degenerative changes in the nervous structures of adrenal medulla were detected in these two groups, while in group 3 these were accompanied by the compensatory-adaptive changes in glandular nervous apparatus. However, despite the pronounced changes found in the nervous structures of adrenal medulla, their function remained high enough, that could be explained by a transition from nervous control of adrenal activity to a humoral one.

[Organization of spinal subpial plexus in man and various animals]. / Organizatsiia subpial'nogo spleteniia spinnogo mozga cheloveka i nekotorykh zhivotnykh.

By means of silver nitrate impregnation and luminescent method adrenergic nervous plexuses in spinal cord of 7 people, 6 dogs, 4 cows and 7 rabbits was studied. 17 serial slices of human and rabbit embryos were also examined. Numerous branching and brightly luminescent adrenergic nerve endings were discovered in composition of nervous plexus of spinal cord subpial layer in man and in animals. They should be thought of as sympathetic endings exerting adaptational and trophic influence on adjacent structures and partly penetrating substantia alba of the spinal cord. These observations broaden the existing conceptions on receptory and effectory neuronal processes on the spinal cord surface.

[Pathomorphologic changes in the sympathetic portion of the autonomic nervous system and cardiovascular pathology]. / Patomorfologicheskie izmeneniia simpaticheskogo otdela vegetativnoi nervnoi sistemy i serdechno-sosudistaia patologiia.

Neurohistochemical and ultrastructural study of the sympathetic innervation of the cardiovascular system indicated its important role in the age alterations and genesis of certain diseases. Early beginning (from the age of 30) of the involution of the heart adrenergic plexus is confirmed in healthy persons. Focal desympathization of the myocardium is detected in sudden cardiac death. A decrease of sympathetic plexus density in zones undergoing atherosclerotic changes is of importance in the genesis of atherosclerosis. In arterial hypertension a primary stage of sympathetic neurones hypertrophy is changed into the phase of the mediators exhaustion in the sympathetic plexus. Myocardiopathies are characterized by progressing myocardial desympathization. An important problem of cardiosurgery is methods of heart reinnervation at its transplantation.

[Age-related changes in the autonomic ganglia]. / Vozrastnye izmeneniia vegetativnykh gangliev.

Ultrastructure of vegetative ganglions (neck-thoracic, intracardial and intestinal) of Wistar and SHR rats, 26-28 months of age was studied electron-microscopically. The most pronounced changes were found in the neck-thoracic ganglions where, apart from lipofuscin deposits, lamellar bodies were frequently found. Redistribution of neuromediators in the neuron body and an increase of the neuroactive substances release into the intercellular space of the ganglion occur with age. The data on possible postsynaptic influence on the presynapse by means of neuromediators are presented. Nissl bodies hypertrophy was observed in the neck-thoracic and intracardial ganglions of old SHR rats.

[Interneuronal interrelationships in autonomic ganglia (the ultrastructural aspects)]. / Mezhneironnye vzaimootnosheniia v vegetativnykh gangliiakh (ul'trastrukturnye aspekty).

Ultrastructural and immunocytochemical results of studies on interneuronal relationship in vegetative ganglia were represented. Age-related changes of synapses (appearance of synaptic type vesicles and smooth endoplasmic reticulum cisterns in postsynaptic terminals), peculiarities of interneuronal links in neurons containing neuropeptide Y and NO-synthase and structural manifestations of non-synaptic interneuronal links were shown. Modern views on interneuronal communications were discussed.

[Ultrastructure of the sympathetic ganglia in hypoxia]. / Ul'trastruktura simpaticheskikh gangliev pri gipoksii.

Short-term hypoxia produces ultrastructural alterations in ganglions of rats in the form of dilatation of some membrane neuron compartments and sinuous plasmatic membrane. More long-term hypoxia produces structural changes of membrane cell components. An increase of lysosome number and lipofuscin granules alternations in chronic hypoxia (1 year) are similar to the age changes and are characterized by intensive accumulation of lipofuscin and Nissl bodies hypertrophy.

[Varying expression of atherosclerosis in the aortic regions with high and low density of the adrenergic nervous plexuses]. / Razlichnaia vyrazhennost' ateroskleroza v uchastkakh aorty s vysokoi i nizkoi plotnosy'iu adrenergicheskikh nervnykh spletenii.

The study was made of early autopsies of 20-55-year-old victims deceased because of trauma. Incubation of sections in 2% glyoxylic acid and luminescent microscopy were used. The density of the adrenergic fibers in the central aortic zones which are most frequently affected with atherosclerosis was 2.8 +/- 0.2%, while in the distal rarely affected zones was 5.0 +/- 0.4%. In the abdominal aorta, the least density (2.1 +/- 2%) of the adrenergic plexuses was over the site of the celiac artery effluence, i.e. at the zones of the intensive atherosclerosis development while the density in the regions slightly affected with atherosclerosis it was 3.8 +/- 0.3%. The results indicate possible permissive role of the sympathetic nervous system in the development of local atherosclerotic alterations.

[The structure of the stellate sympathetic ganglia under long-term hypoxia]. / Stroenie zvezdchatykh simpaticheskikh gangliev v usloviiakh dlitel'noi gipoksii.

Changes of mitochondrial ultrastructure indicating not only degenerative processes but also the presence of organelle adaptive reactions were demonstrated in sympathetic neurons. Appearance of osmiophilic inclusions in mitochondrial matrix relates to most typical organelle alterations in ageing. Number of smooth endoplasmic reticulum vesicles equal in size to synaptic vesicles of nerve cells processes grows higher. Such vesicles are usually located near postsynaptic active zones and areas with neuronal plasmolemma free from glia. Their outward resemblance does not allow to claim that neuromediators and neuromodulators may turn up in these vesicles, although dendrites contain and may release certain biologically active substances. Basic difference between 24 and 30-months old rats lies in earlier degenerations of nerve cells in old animals. Forming of dark granules may be also associated with conditions of fixation. Small granular (SG) cells lacked typical lipofuscine granules, while their ultrastructure changed insignificantly. SG cells capacity to divide mitotically in functional maturity is likely to be one of the possible explanations of such difference.

[The phenomenon of focal sympathetic denervation of the major vessels in the development of atherosclerosis]. / Fenomen ochagovoi desimpatizatsii magistral'nykh sosudov pri razvitii ateroskleroza.

22 aortas obtained from people aged 20-55 who died in accidents by early dissections were studied. Adrenergic nerve plexuses of aortal wall were examined by quantitative neurohistochemical method. Focal reduction of indexes of these plexuses density was defined by the age of 30. The process of desympathization runs unevenly with nerve plexuses from zones of aorta cranial to areas of its branching altered to greater extent. This very zones are subjected to atherosclerosis selectively. We tend to consider the process of desympathization for one of atherosclerosis factors developing in vascular wall zones with the loss of adaptive-trophic influence of the vegetative nervous system sympathetic activity.

Inclusions similar to Hirano bodies in urinary bladder neurons of dogs.

Unusual intracytoplasmatic inclusions were found in urinary bladder neurons in dogs. The plate-like inclusions were composed of thin filaments, and when viewed en face, appeared as oval or angular bodies with regular lattice work array. When viewed in a transverse section, they were of rod-like shape and were composed of longitudinal filaments and transverse bars. The inclusions were observed in all ganglia of the urinary bladders studied. Three-dimensional reconstruction of the inclusions was made, using a tilting device. By means of this reconstruction, it could be demonstrated that their ultrastructure is similar to that of Hirano bodies which occur in human neurons of the central nervous system in cases of neurodegenerative diseases. The authors suggest that unusual intraneuronal inclusions represent a peculiarity in cytoskeletal protein assembly typical of canine urinary bladder neurons.

Intracellular penetration of ruthenium red in embryonic nervous tissue.

Electron microscopic investigations, using ruthenium red revealed that dye is usually observed in immature neuronal cells in autonomic ganglia of rat embryos and fetuses. Ruthenium red does not penetrate undamaged neurons in mature ganglia. Ruthenium red positive material covers neuronal cell plasmalemma even in early primordial phases of autonomic ganglia. Plasmalemma of growth zones does not react with ruthenium red. Intracellular penetration of immature neurons by ruthenium red, according to expectation, depends on damage to cell membrane due to the fixation procedure, especially in the growth zones.