Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation

The first-order sensory relay for olfactory processing, the main olfactory bulb (MOB), retains the ability to acquire new interneurons throughout life. It is therefore a particularly appropriate region for studying the role of experience in sculpting neuronal networks. We found that nostril closure decreased the number of newborn granule cells in the MOB, the complexity of their dendritic arborization, and their spine density, without affecting the preexisting population of granule cells. Accordingly, the frequency of miniature synaptic inhibitory events received by mitral cells was reduced. However, due to a compensatory increase in newborn granule cell excitability, action potential-dependent GABA release was dramatically enhanced, thus counteracting the reduction in spine density and leading to an unaltered synchronization of mitral cell firing activity. Together, this study reveals a unique form of adaptive response brought about exclusively by the cohort of newborn cells and used to maintain normal functioning of the MOB.     

Reactions of neural elements of neocortex to action of hypoxia at the early neonatal period in rats

We studied reactions of neural elements from different neocortex regions (sensorimotor, visual, auditory) to acute normobaric hypoxia on the model of human incomplete pregnancy (the 2-day-old rat pups) and revealed similar and unidirectional reorganization in all these regions. The chosen parameters of hypoxia induced the earliest detectable changes as fast as in a day since exposure: a decrease in cell body size and cytoplasmic volume, intensification of apoptotic cell death. By the end of the neonatal period (day 5), several ultrastructural changes were observed by indicating deceleration of processes of nerve cell differentiation: arrest of complication of smooth and rough endoplasmic reticulum and Golgi apparatus, the reduced number of free ribosomes and polysomes in cytoplasm as well as of axonal and dendritic growth cones in neuropil, delayed and disordered myelination of nerve fibers. All these morphofunctional abnormalities may be the structural basis for development of neonatal encephalopathies.     

Distribution of GAD67-expressing neurons and morphological changes in hippocampal structures during pubertal period after acute perinatal hypoxia in rats

We investigated structural changes in the Wistar rat hippocampal CA1 field and fascia dentate during the pubertal period (on P60) after perinatal hypoxic exposure as well as the distribution of GAD67-expressing neurons in these structures. It was established that in the granular layer of the fascia dentata and in the CA1 field acute perinatal hypoxia leads to irreversible homotypic abnormalities as expressed in the reduced number of neurons and their rows as well as injury of a considerable portion of cells, which exhibit the signs of chromatolysis and vacuolization of the cytoplasm. Both in experimental and control animals, GAD67-expressing neurons in the fascia dentata are scattered diffusely and share approximately the same size of their populations. In the CA1 field, immunoreactive neurons lie in the lower rows of the pyramidal layer, while neurons in the upper layers exhibit no immunolabeling and have less synaptic structures in experimental animals than in control. We suggest that neurons in the hippocampal structures are involved in the regulation of functions and formation of prenatal pathology.     

Effect of hypoxia in early perinatal ontogenesis on behavior and structural characteristics of the rat brain

The study has shown that acute hypoxia in newborn rat pups can lead to disturbances in processes of formation of brain structures, behavior reactions, and learning in the subsequent ontogenesis. The single normobaric hypoxia at the 2nd day of life causes retardation of such integrative parameter or general development and growth as body mass at the period of feeding. In such animals, essential disturbances of the sensorimotor development were revealed in forms of delay of reflex reactions of turning on a plane, negative geotaxis, and avoidance of edge. Also detected was action of hypoxia on hanging on a rope by using front legs (a symptom of muscle weakness). Morphological study has shown all studied functional zones of neocortex (motor, sensomotor, auditory, visual) to response stereotypically to the early postnatal action of hypoxia. The death of nerve cells is predominant in the II–III associative layers, the sizes and number of pyramidal neurons are sharply decreased. Different hippocampus fields maturing after death in mammals show a characteristic response to hypoxia. In individual hippocampus fields there was detected a different degree of death of neurons, with predominance in the CA3 and CA4 fields. A possibility of modeling the perinatal encephalopathy with minimal brain dysfunctions in children is discussed.     

Change of the neocortex nervous tissue in rat ontogenesis after hypoxia at various terms of embryogenesis

The performed study has shown that in rats submitted to hypoxia (3 h, 7% O2) at the 14th day of embryogenesis (E14) as compared with control animals, density of disposition of cells in the brain cortex decreased for the first month of postnatal ontogenesis (maximally by 40.8% by P20). In dying neurons, swelling of the cell body, lysis of organoids, and disturbance of the cytoplasmic membrane intactness were observed. Two waved of neuronal death by the mechanism of caspase-dependent apoptosis were revealed; the first involved large pyramidal neurons of the V layer (P10-20), the second--small pyramidal and non-pyramidal neurons of the II--III layers (P20-30). In neuropil of molecular layer, a decrease of the mean amount of labile synaptopodin-positive dendrite spines was observed, as compared with control. In rats exposed to hypoxia at E18, no changes of cell composition and structure of the nervous tissue were found in the studied brain cortex areas. Thus, formation of the cortex nervous tissue in postnatal ontogenesis of rats submitted to hypoxia at the period of neuroblast proliferation-migration is accompanied not only by a change of the cell composition of various cortex layers in early ontogenesis, but also by a decrease of the number of the synaptopodin-positive spines in molecular layer, the decrease being preserved in adult animals.     

Changes in the cerebellum of the rat after actinomycin during the postnatal period]

A single dose of actinomycin was applied to young Wistar albino rats in the critical phase of their cerebellar development. The morphological alterations of the cerebellar cortex were studied by means of light and electron microscopy on several postnatal days. The cell types of the cerebellar cortex reacted in different ways toward the noxious substance according to their stage of development. The acute alterations consisted of an edematous reaction of the neuronal and glial perikarya (light degeneration) and a shrinkage of the neurons (dark degeneration). A massive intercellular edema and a rarefaction of glia cells as well as the Purkinje cell fibres proved to be the long-term damage. This pattern of the alteration was discussed regarding the chemodifferentiation of the cells of the cerebellar cortex, the onset of cerebellar function on day 14, and the establishment of a neuroglial functional unit.     

Structural changes in the neocortex nervous tissue in rat ontogenesis after hypoxia at various terms of embryogenesis

The performed study has shown that in rats submitted to hypoxia (3 h, 7% O₂) at the 14th day of embryogenesis (E14) as compared with control animals, density of distribution of cells in the brain cortex decreased for the first month of postnatal ontogenesis (maximally by 40.8% by P20). In dying neurons, swelling of the cell body, lyses of or ganoids, and disturbance of the cytoplasm membrane intactness were observed. Two waves of neuronal death by the mechanism of capsize-dependent apoptosis were revealed; the first involved large pyramidal neurons of the layer V (P10–20), the second-small pyramidal and non-pyramidal neurons of the layers II–III (P20–30). In neurosis of molecular layer, a decrease of the mean amount of labile synaptopodin-positive dendrite spines was observed, as compared with control. In rats exposed to hypoxia at E18, no changes of cell composition and structure of the nervous tissue were found in the studied brain cortex areas. Thus, formation of the cortex nervous tissue in postnatal ontogenesis of rats submitted to hypoxia at the period of neuroblast proliferation-migration is accompanied not only by a change of the cell composition of various cortex layers in early ontogenesis, but also by a decrease of the number of the synaptopodin-positive spines in the molecular layer, the decrease being preserved in adult animals.     

Periodization of the early postnatal development in the rat with particular attention to the weaning period

The early postnatal period is characterized by a great plasticity with critical windows in which any inadequate insult or intervention may be able to influence both positively and adversely postnatal growth and development. After birth the rat littermates enter the presuckling period (initial 6 hours terminated by the first nursing), characterized by transition from the amniotic fluid to the air, by the changes of the ambient temperature, by the termination of placental nutrition and by oxidative stress. After this stage the suckling period initiates and the littermates start to consume milk of their mothers. Comsumption of milk culminates on day 15, then decreases and terminates on postnatal day 28. The end of the suckling period and the onset of physiological weaning is determined by the moment when the youngs for the first time consume the solid food together with milk (postnatal day 17 in rats). On day 19 the first intake of drinking water occurs. The weaning period terminates by the last consumption of maternal milk - on postnatal day 28. It is necessary to stress that the duration of early postnatal periods is independent of the changes of body weight. The precise knowledge of individual ontogenetic periods critical for further development is crucial for the prediction and explanation of reactions to various pathogenetic stimuli both under experimental conditions and in clinical medicine.     

The remote consequences of hypoxia influence in perinatal development period on structurally functional characteristics of the rat brain

The study has shown that influence of acute hypoxia in perinatal period leads to structural changes in motor and visual of the neocortex for 20 postnatal days in the form of disturbance of the structural organisation of the neocortex layers. Different fields of hippocampus in perinatal period differently react to hypoxia, and evidence of existence of a long-term perinatal hypoxia was obtained. It is established that after action of acute hypoxia in all the fields there is a cellular destruction, and thinning of pyramidal neurones layers. The most expressed cellular destruction takes place in fields CA4 and CA3. In process of augmentation, the destruction of cells remains appreciable in the field CA4, reduced in the field CA3 and not found in the field CA1; however, in fascia dentate, the destruction of granular neurones with age augmentation increases. Along with in reduction of the dimensions of cellular bodies pyramidal neurones in all fields of hippocampus takes place. Also in all fields of hippocampus, activation of astrocytic reaction occurs, more expressed in the field CA4. The hypoxia influence in the early postnatal period can affect synaptogenes, particularly the formation of giant synapses in a dentate fascia. Study of functional features of the excitatory system of such animals has shown that hypoxia can induce appreciable disturbances of behavioural responses. In rats, disturbances of inhibiting functions of the cerebral cortex, raised anxiety, and spatial learning and working memory disturbances have been noted.     

Kinetic properties of rat heart cathepsin D under normal conditions, during emotional-pain stress and in the post-stress period]

Cathepsin D preparations have been isolated from the heart of healthy animals and stress-surviving rats by the method of affine chromatography with the hemoglobin-biogel-P300 sorbent. To analysis of the obtained data permits concluding that acute stress stimulates activation of the catalytic function of cathepsin D in the heart. But the period after the stress accompanied by the consecutive proteolysis rate reduction, that can be explained, probably, by a change in enzyme conformation. The concentration of Ca2+ (10(-6), 10(-5) M) and cAMP (10(-7), 10(-6) M) exert a regulating influence on the cathepsin D activity in the heart in acute stress period and after it.     

Long-term effects of perinatal hypoxic exposure on microvascular endothelium in the rat neocortex

The long-term effects of perinatal hypoxic exposure followed by the administration of salifen, a GABA derivative, on morphological characteristics of the vascular wall elements in the neocortical microvasculature were studied in rats. Salifen, when applied at therapeutic doses, was established to exert an endothelial protective effect. It prevents such typical pathomorphological consequences of perinatal hypoxia as endothelial hypertrophy, the appearance of multiple intravascular endothelial outgrowths, narrowing of the capillary lumen, malformation of the lamina densa, swelling of perivascular astrocytes, and reactive changes in pericytes. In all neocortical layers, a density of blood vessel distribution across microvasculature as well as their cross-sectional area were found to be approximately the same in adult animals both in control and after hypoxic exposure followed by salifen administration. Changes and rearrangements in the capillary bed after hypoxic exposure and salifen administration were shown to occur at earlier developmental stages, while by the maturity period the structural parameters of microvasculature become stabilized. The endothelial protective effect of salifen promises high clinical efficiency of this preparation and serves as a basis for further studies in this direction.