Pulmonary vascular resistance in adult rats exposed to hypoxia in the neonatal period

Newborn rats were exposed to hypoxia (10% O2 + N2) from 24 h to day 6 of neonatal life and then returned to room air until 45 days of age (experimental). The rats were anaesthetized, heparinized, and exsanguinated. The chest was opened and the lungs were perfused with diluted autologous blood at a constant flow rate (Q). The pulmonary arterial pressure (Pa) and venous pressure (Pv) were monitored. The properties of the pulmonary vasculature were assessed by measuring baseline vascular resistance, PVR = (Pa-Pv)/Q, segmental pressure gradients (double occlusion technique), pressure-flow relationship, hypoxic pressor response (HPR, 3% O2), and the response to 0.5 microgram bolus of angiotensin II (AII). These were compared with similar measurements on age-matched control animals never exposed to hypoxia. The perfusate hematocrit and gases were not significantly different between the two groups. The PVR normalized to body weight was 30% higher in the experimental groups (p less than 0.005). The double occlusion results (obtained at a flow rate of 13 mL/min) revealed that this increase in resistance was primarily due to the increase in the postcapillary resistance. HPR was primarily in the upstream segment in both groups but was larger in the experimental group. In contrast, the response to AII occurred in both the upstream as well as in the downstream vascular segments and did not differ between the two groups. We conclude that adult rats exposed to hypoxia in the neonatal period have elevated pulmonary vascular resistance and increased vascular reactivity to hypoxia.     

Architectonics of GABAergic inhibitory network in the sensorimotor area of the rat neocortex in the early postnatal period under normal conditions and after acute perinatal hypoxia

The distribution of GABAergic interneurons as well as terminal and synaptic networks in different layers of the rat sensorimotor neocortex were studied at different stages of the postnatal period under normal conditions and after exposure to perinatal hypoxia. In control animals, the architectonics of the inhibitory network in different layers of the sensorimotor neocortex was shown to display distinctive features at different stages of the postnatal development. At early postnatal stages, a significant portion of neurons in layers II–V are immunopositive for GAD-67, indicative of a high level of GABA expression, however, GABA transmission is extremely weak, thus supporting the presence in the neuropil of only sporadic GABAergic terminals and synapses. By the juvenile age, a dramatic drop in the number of GABAergic neurons and an increase in the density of the network of GABA-immunopositive processes and synaptic structures occur in the neuropil, suggesting a considerable increase in GABA transmission. A higher level of GABA transmission is revealed in layers IV and V, persisting over the prepubertal period. Our results demonstrate that acute perinatal hypoxia affects the state of the inhibitory GABAergic network in the rat sensorimotor neocortex during the postnatal period. GABA expression and transmission were shown to change virtually in all layers.     

Electrical activity of the neocortex in adult rats after prenatal hypoxia and in epilepsy model

Changes in electrical activity of the neocortex after prenatal hypoxia (day 14 of embryogenesis, E14, 7% O₂ for 3 h) and intracortical microinjection of epileptogenic 4-aminopyridine (4-AP) were studied in adult (3-month-old) rats. The frequency–time parameters of electrocorticogram (ECoG) were analyzed during sleep and wakefulness as well as in a model of 4-AP-induced spike-wave discharge (SWD) epileptiform activity. The results showed that in rats exposed to prenatal hypoxia the theta rhythm had a lower frequency while sleep spindles displayed a lower spectral power in the low-frequency range as compared to the control group. In rats with prenatal pathology, there was revealed a delayed onset of epileptiform activity and a shifted frequency distribution of the SWD spectral power induced by 4-AP.     

Thermoregulation characteristics of rats exposed to cold in the early postnatal period

Cold adaptation of adult rats (at 4-5 degrees C for 7 weeks) increased their ability to respond to noradrenaline by the rise of body temperature and heat radiation, led to an almost 2-fold increase in the relative brown fat mass (BFM). Adult rats which experienced cold imprinting (from the first to the seventh day after birth, 15 min at 4-5 degrees C) showed a far less increment of the BFM on cold adaptation, no additional rise of body temperature and heat radiation in response to noradrenaline. In cold-imprinted rats, the relative surface of the tail and the body surface heat radiation transfer conefficient were found to be reduced. This attests to stable adaptive changes in physical thermoregulation, directed toward increase in animals' heat insulation.     

Peculiarities of H3-muscimol binding to neocortex membranes of rats exposed to the effects of ethanol in the prenatal period

White rats were subjected to ethanol exposure during 5-20 days of pregnancy. 3H-muscimol binding with synaptosomal neocortex membranes yielded from two month age offsprings was studied. 3H-muscimol binding level for experimental animals was 27% more than for control ones. Possible ways of GABAergic system malformation are discussed.     

Effect of adaptation to hypoxia on the resistance of rats to the epileptogenic action of penicillin

The influence of adaptation to moderate hypoxia on anticonvulsive resistance of low tolerant rats has been investigated. Focal epilepsy was induced by penicillin application to sensorimotor cortex of the rat brain. Adaptation to hypoxia has been shown to increase the resistance of rats to epileptogenic penicillin effect which is manifested in the prolongation of the latent period of epileptiform discharges and less frequent epileptic fits. The mechanisms of the resistance increase remains to be investigated.     

Excitability changes of cortical neurons during the postnatal period in rats exposed to prenatal hypobaric hypoxia

Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are 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.     

Comparative analysis of ECG characteristics in pregnant rats subjected to acute hypoxia in the period of organogenesis

Various ECG characteristics are investigated in white rats subjected to acute hypobaric hypoxia on the 9th–10th day of gestation corresponding to the period of organogenesis. The hypoxia-induced changes in the ECG characteristics are different in groups with a low, middle, and high resistance to acute hypoxia.     

Pitfalls in the etiological diagnosis of congenital adrenal hyperplasia in the early neonatal period

The plasma levels of 8 steroid hormones were studied longitudinally in 20 newborns affected with either 21-hydroxylase (21-OH), 11-hydroxylase (11-OH) or 3 beta-hydroxysteroid deshydrogenase (3 beta-ol) deficiencies during the first month of life. Comparison was also made between the patterns observed according to age at first examination (n = 13 before 8 days of age) and the type of the enzymatic block. The most striking findings were the variability in hormone levels and/or evolution with age and the difficulties in making a definite positive or etiological diagnosis at first examination. In some newborns with untreated 21-OH deficiency, 17 alpha-hydroxyprogesterone levels may start off within the normal range or not so far above it. Also, levels of unconjugated dehydroepiandrosterone and other delta 5 steroids may be so high during the first week of life in all 3 forms that an erroneous diagnosis of 3 beta-ol deficiency could easily be considered. In several cases the etiological diagnosis was only ascertained by multiple steroid determination and/or dynamic tests. These discrepancies were not found in infants studied later on in life. It thus appears that a peculiar steroid pattern is observed in the immediate postnatal period in babies with various enzyme defects, which might be related to the morphological changes occurring in the adrenal cortex at this age.