Changes in the ultrastructure of the adrenal medulla and cortex during endotoxic shock

Electron microscopy of the adrenal medulla and cortex during the intermediate period of endotoxin shock has revealed severe destructive changes in parenchymal cells. These changes are the reason for synthetic, secretory and trophic disturbances of glandular functions. Ultrastructural lesions indicate that stress exposure exceeds the adaptive capacity of cells, the majority of which are exhausted and killed.     

Correlation of the destructive and reparative processes in neurons of the cerebral cortex in rats after thermal injury

Rat brain sensorimotor cortical neurons were investigated in thermal trauma, using electron microscopic radioautography. RNA synthesis and destructive neuronal changes (chromatolysis, nuclear and mitochondrial damage) have been determined. It has been established that the development of a reparative process--ribosomal RNA synthesis--was roughly parallel to the appearance of destructive changes and was marked in neurons with considerable ultrastructural disturbances.     

Structural/functional disturbances in the rat sensorimotor cortex evoked by low-intensity environmental factors

The effect of low-frequency continuous vabration, hypokinesia, and shielding from the geomagnetic field were studied on 424 albino mongrel male rats. The action of these low-intensity factors of a different nature caused changes first of all in the microcirculatory bed (MCB) of the cerebral cortex. Structural disturbances, as well as the disturbances of redox metabolism in the neurons appeared close to those observed during hypoxia of a different origin; they obviously resulted from the disturbances of the MCB functions, which caused discrepancy between the needs for energy supply and the transport system state. Specificities of the disturbances evoked by different factors can be related to desynchronization of the biorhythms (e.g., caused by deprivation of the geomagnetic field).     

Early effects of the influence of ionizing radiation in relatively small doses on the neuromediator systems responding to the central regulation of the hypothalamo-pituitary-adrenal cortex system

In experiments with mature Wistar male rats changes of mediator interrelations in different brain parts, responsible for the central regulation of the hypothalamo-pituitary-adrenocortical system, were detected at early times after whole-body X-irradiation with a dose of 12.9 mC/kg. These changes represent one of the major mechanisms leading, at later times after irradiation, to the development of syndromes related to diencephalic disturbances.     

Ultrastructure of sensorimotor cortex neurons in the progeny of rats receiving alcohol during pregnancy

Dynamics of ultrastructural changes in the sensomotor cortex neurons has been studied on the 21st, 30th and 60th days of life in offspring born by the rats given 20% alcohol (2 g/kg) during pregnancy. Moderate antenatal alcoholization produces certain disturbances in the ultrastructure of the cortical neurons and their dendrites. This is manifested as presence of retardation signs in maturation of nervous cell populations, as dystrophic changes in the neurons and their dendrites and display of reparative character with their own dynamics in the postnatal period of ontogenesis. The first two categories of the ultrastructural changes in the cortical neurons are more manifested at early stages of the postnatal development of the offspring, and the reparative processes--at the age of two months. Despite the presence of the reparative shifts, the dystrophic changes of the neurons of hypoxic character are present up to the period of sexual maturation. This demonstrates that the antenatal alcoholic intoxication in the offspring is manifested in the postnatal ontogenesis for a long time.     

Ultrastructure of the cerebral cortex in the rat after the effect of electromagnetic impulse

In mature rats an area on the head has been subjected to a single radiation for 1.5 sec with microwaves in the continuous regimen of generation, frequency 2.4 GHz level of the specific absorbed power 5 W/g, that is accompanied with appearance of convulsions. Under anesthesia specimens of the superficial layer of the cerebral superlateral part are taken and subjected to electron microscopical investigation. Immediately after radiation and in 2 h certain disorders in microcirculation and reactive changes of mitochondria in perikaryons, axons, dendrites, synapses of the neurons and in gliocytes are revealed. The mitochondrial changes are designated as "edematous". In 2 and 6 h in karyoplasm of some neurons membranous structures appear; they are interpreted as a result of heat denaturation of the nuclear proteins. In synapses, together with lesions of mitochondria, synaptic complexes undergo destruction and osmiophilic substance is accumulated in the subsynaptic zone along the whole length of the contact. In one day, essential destructive changes are revealed as severe lesions of some neurons, vacuolization and destruction of mitochondria, localized in all the structures. Pathogenesis of the neurological disturbances is based on disturbances of interneuronal interactions, connected with an immediate heat effect of the electromagnetic radiation on the structures responsible for the synaptic transmission and with a rapidly developing tissue hypoxia as a consequence of microcirculatory disturbance and a sharp inhibition of energetic metabolism.     

Ultrastructure of the cerebral cortex and hippocampus of rats in the early postresuscitation period following total ischemia

The rat frontal brain cortex and CAr hippocampal region were studied on the 4th day after 10-min complete ischemia. It has been established that the number of "dark" osmiophilic neurons was increased. The reparative, destructive and adaptive processes in cells were observed. The most prominent destructive changes were found in CAr hippocampal region, they can be associated with the microcirculatory disturbances. The hypertrophic thread-like mitochondria appear in the nervous and glial cells, with the quantity of lipofuscin granules increasing. Lipofuscin and hypertrophic mitochondria are thought to provide energy exchange in the brain cells during the postischemic period, forming one of the mechanisms of intracellular adaptation to hypoxia.     

Ultrastructural changes in the cerebral cortex of an 100 1/2-year-old man

Age changes in fields 39 and 40 (after Broadman) have been studied in a 100 years and 6 months old man died from peritonitis resulted from the surgical intervention, performed in connection with strangulation of the hernia. In the medical history there were no ++neuro-physical signs. The material was taken in 1 h 15 min after clinical death had been stated. The results obtained have been compared with those studied in the brain of persons, who had not yet reached the age of 100 years and had not any signs of ++neuro-physical disturbances and died after urgent surgical interventions in the abdominal cavity. In this group of persons the material for investigation was taken in 15-30 min after clinical death had been stated. The technique for treatment the material, its preparation for electron-microscopical examination is identical. Immersion fixation has been applied. The material obtained from an old animal fixed by means of vital perfusion of 2.5% glutaraldehyde solution is also used. In the person of 100 years and 6 months old the changes do not practically differ from those obtained from persons of younger age, however, the time from the statement of clinical death up to obtaining the material essentially influences preservation of the synaptic apparatus components.     

Spontaneous and evoked activities of interpositus nucleus neurons before and after lesion of the cerebellar cortex

Spontaneous and evoked activities of nucleus interpositus neurons (IN) of the cerebellum were examined before and after cerebellar paravermal cortex lesions in cats anesthetized with alpha-chloralose. It was found that spontaneous activity increased dramatically following cortical ablation: before the lesion only 4% of cells encountered fired at a rate exceeding 80 impulses/sec., whereas up to 40% discharged at this rate postoperatively. Responses to paw stimulation were also altered: the initial excitation was lengthened from 8.5 to 15.8 msec; narrow; trough causing segmentation in this excitation, which seems to result from Purkinje cell inhibition, was absent; and the succeeding inhibitory period was reduced in duration by 50%. Also after the lesion there was a strong tendency for the neurons to discharge in bursts. It is suggested that changes in cell activity in the IN following cortical lesion unveil neural mechanisms of motor disturbances in lesioned cats.     

Post-irradiation changes in the content of phospholipids and cyclic nucleotides in the mouse brain]

The effect of ionizing radiation (5, 20, 100, 200 and 400 Gy) on the content of phospholipids and cyclic nucleotides in the brain tissue has been studied in experiments on albino mice. During the development of evident behavioural disturbances in irradiated mice (2 h after irradiation with doses 100-400 Gy), significant changes were observed in the content of phosphatidylinositides and cyclic GMP. These changes may account for disturbances in the function of the central nervous system during cerebral forms of acute radiation injury.     

Modification of redox sites of N-methyl-D-aspartate receptors affects changes in bioelectrical activity of olfactory cortex slices induced by anoxia in rats

The effects of the thiol oxidative agent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) inhibiting NMDA receptors activity on changes of the evoked focal potentials generation (the NMDA and non-NMDA components EPSP) in response to long-term (LA) and short-term (SA) anoxic exposure which induced functional disturbances or promoted increasing of neurons resistance to LA, were studied on the rat olfactory cortex slices (Wistar-Kyoto). It was revealed that DTNB (200 mkM) effectively protected the depression of the EPSP generation induced by LA in the most tested neurons. In addition, DTNB eliminates the protective effect of the SA on focal EPSP generation evoked by LA. Nevertheless this dependence concerns the NMDA component and, to a lesser extent, the non-NMDA component EPSP. A possible role of changes of the NMDA receptor modulatory redox sites in mechanisms of functional disturbances and increasing neuronal resistance induced by hypoxic influences, is discussed.     

Effect of visual deprivation on evoked potentials in the visual cortex and superior colliculus in rabbits

Evoked potentials arising in the visual cortex and superior colliculus to stimulation of the collateral eye by single, paired, and repetitive flashes were recorded in rabbits reared in darkness or in normal illumination. The absence of significant change in the latent period and amplitudes of the first two components of the collicular responses and of the recovery cycle and response to repetitive stimulation in the light-deprived animals suggest that photic stimulation does not affect the normal functional development of the rabbit retinotectal system. However, functional deafferentation in the early postnatal period gives rise to serious disturbances of visual cortical function, as reflected in a marked decrease in amplitude of the primary response, lengthening of the recovery cycle, and narrowing of the range of rhythm-binding frequencies of flashes. These disturbances were reversible. The period of maximal sensitivity of the rabbit retinocortical system to visual deprivation begins at the end of the first month of postnatal life. The possible mechanisms lying at the basis of these functional disturbances in light-deprived animals are discussed.     

Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock.

The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock.     

Conditioned reflexes following unilateral damage to the premotor cortex and the dorsal portion of the head of the caudate nucleus in dogs

The study was carried out on dogs by the secretory-motor method with a two-side reinforcement. Simultaneous and unilateral lesion of the premotor cortex and of the dorsal part of the caudate nucleus head brought about prolonged disturbances of the vegetative components (pulse and respiratory rate) and in the choice of the side of food reinforcement. The change in the magnitude of conditioned salivation, latencies of secretion and motor reaction was temporary, and by the end of the third postoperative period their initial magnitudes were restored. The duration of the disturbances of higher nervous activity depended on the localization and extent of lesion of the caudate nucleus head. Tests were made with chlorpromazine and caffeine before and after the lesion of the brain structures. The tests in the postoperative period revealed latent disturbances in the dog higher nervous activity. It is assumed that the premotor cortex and the dorsal part of the caudate nucleus head are one of the sub-systems involved in the regulation of vegetative, somatic components of unconditioned behaviour and in the analysis of conditioned stimuli.     

What is the role of disturbance in catalyzing spatial shifts in forest composition and tree species biomass under climate change?

Mounting evidence suggests that climate change will cause shifts of tree species range and abundance (biomass). Abundance changes under climate change are likely to occur prior to a detectable range shift. Disturbances are expected to directly affect tree species abundance and composition, and could profoundly influence tree species spatial distribution within a geographical region. However, how multiple disturbance regimes will interact with changing climate to alter the spatial distribution of species abundance remains unclear. We simulated such forest demographic processes using a forest landscape succession and disturbance model (LANDIS-II) parameterized with forest inventory data in the northeastern United States. Our study incorporated climate change under a high-emission future and disturbance regimes varying with gradients of intensities and spatial extents. The results suggest that disturbances catalyze changes in tree species abundance and composition under a changing climate, but the effects of disturbances differ by intensity and extent. Moderate disturbances and large extent disturbances have limited effects, while high-intensity disturbances accelerate changes by removing cohorts of mid- and late-successional species, creating opportunities for early-successional species. High-intensity disturbances result in the northern movement of early-successional species and the southern movement of late-successional species abundances. Our study is among the first to systematically investigate how disturbance extent and intensity interact to determine the spatial distribution of changes in species abundance and forest composition.     

Cholinergic receptor alterations in the cerebral cortex of spinal cord injured rat

Many areas of the cerebral cortex process sensory information or coordinate motor output necessary for control of movement. Disturbances in cortical cholinergic system can affect locomotor coordination. Spinal cord injury causes severe motor impairment and disturbances in cholinergic signalling can aggravate the situation. Considering the impact of cortical cholinergic firing in locomotion, we focussed the study in understanding the cholinergic alterations in cerebral cortex during spinal cord injury. The gene expression of key enzymes in cholinergic pathway - acetylcholine esterase and choline acetyl transferase showed significant upregulation in the cerebral cortex of spinal cord injured group compared to control with the fold increase in expression of acetylcholine esterase prominently higher than cholineacetyl transferase. The decreased muscarinic receptor density and reduced immunostaining of muscarinic receptor subtypes along with down regulated gene expression of muscarinic M1 and M3 receptor subtypes accounts for dysfunction of metabotropic acetylcholine receptors in spinal cord injury group. Ionotropic acetylcholine receptor alterations were evident from the decreased gene expression of alpha 7 nicotinic receptors and reduced immunostaining of alpha 7 nicotinic receptors in confocal imaging. Our data pin points the disturbances in cortical cholinergic function due to spinal cord injury; which can augment the locomotor deficits. This can be taken into account while devising a proper therapeutic approach to manage spinal cord injury.     

Age aspects of receptor-effector reactions and the regulation of adenylate cyclase activity

The present-day notions on the trends and mechanisms of changes in the activity of the cyclic nucleotide system are considered in the age aspect. Their role in disturbances of the neurohumoral regulation processes at the molecular level is discussed. Biochemical mechanisms of changes in the receptor-effector reactions are analyzed. An analysis of these changes is very important for elucidating general regularities of the cyclase system functioning with disturbances of biochemical regulation at the membrane and cell levels.     

Biochemical and morphofunctional changes in the myocardium of dogs with occlusion of the terminal portion of the aorta

The occlusion of the terminal aortic region was experimentally induced in 48 dogs. It has been shown that myocardial lesions localized predominantly in the papillary muscles and subendocardially appear already 3 hours after the occlusion. The number of the affected cardiomyocytes increases and their size enlarges. The duration of ischemia directly correlates with metabolic disturbances: changes in the function of adenylate cyclase system, ion imbalance, damages in the energy metabolism. Metabolic and morphologic changes are accompanied by disturbances in the cardiac function manifested in the decrease of myocardial contractility.     

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.     

Role of brain noradrenergic mechanisms in disturbing the circadian rhythm of the functioning hypothalamo-hypophyseo-adrenal cortex system in white rats in early ontogeny

The effects of hormone action and disturbance in catecholamine synthesis in the early postnatal ontogenesis on the circadian rhythm in the hypothalamic-hypophysial-adrenocortical system function were compared in the adult albino rat males. Injection of prednisolone on the 17-19th days of life blocked completely the diurnal rhythm of the corticosterone basal level in blood, the rhythm of adrenocortical response to an emotional stressor and to injection of noradrenaline into the brain lateral ventricle in 3-4 month old animals. Injection of an inhibitor of tyrosine hydroxylase, alpha-methyl-p-tyrosine, at the same period resulted in disappearance of the diurnal rhythm of the corticosterone basal level in adult animals, although the rhythm of response to an emotional stressor or injection of noradrenaline into the brain remained unchanged. A conclusion has been reached that disturbances in catecholamine synthesis in the early postnatal period induces long-term changes of predominantly tonic corticosterone secretion, while the hormone action on the circadian rhythm of the corticosterone basal level and stress response is only partly due to changes in noradrenergic regulation of the hypothalamic-hypophysial-adrenocortical system.