The brain is one of the most important sources of dopamine in general circulation during perinatal ontogenesis in rats

This study was aimed to test our hypothesis that dopamine synthesized in the neurons of the brain is delivered to the general circulation in rats during prenatal and early postnatal periods, i.e. before the establishment of the blood-brain barrier. Using the high performance liquid chromatography, it was demonstrated that the dopamine concentration and content in the peripheral blood in fetuses and neonatal rats (i.e. before the establishment of the blood-brain barrier) greatly exceeded those in adult rats. Moreover, the establishment of the blood-brain barrier was accompanied by the significant increase of the dopamine concentration in the brain. A drop of the dopamine concentration in fetal plasma after the microsurgical lesion of the forebrain and mesencephalon (encephalectomy) are considered as direct evidence in favour of our hypothesis.     

Different uptake and handling of oleoyl-estrone by fetuses and neonatal rats.

To determine whether oleoyl-estrone can be transferred from mothers to their offspring either during pregnancy or lactation, a gavage of tracer dose of (3)H-Oleoyl-estrone was given to 21-day pregnant rats and to lactating rats on day 15 after delivery. In pregnant rats, the label was found in maternal blood as well as in liver and fetal serum, the latter showing the highest specific activity observed. In lactating rats, oleoyl-estrone label was found both in the mammary gland and maternal serum; in the pups, label was found in their stomach contents (i.e., clotted milk) and serum. The results suggest that the placenta effectively blocks the passage of oleoyl-estrone to the fetuses probably because of its high esterase activity. On the other hand, oleoyl-estrone is easily transferred from dams to pups, as a component of milk.     

The agonists of I-A serotoninergic receptors restore in rats behavior impaired by L-dihydroxyphenylalanine

The ability of selective and nonselective 5-HT1A agonists, nondirect 5-HT agonists and 5-HT2 antagonists influence on the L-DOPA-disturbed rats behaviour were studied. The results indicate that agonists 5-HT1A like receptors largely than 5-HT2,3 agonists, 5-HT2 antagonists and nondirect 5-HT agonists promote restoration of the L-DOPA disturbed escape behaviour in acute stress situation.     

Effect of L-dihydroxyphenylalanine on rat behavior and on catecholamine metabolism of the brain in rats with different degrees of emotional-behavioral reactivity

The effect of L-DOPA in combination with benserazide (Madopar), administered intraperitoneally on the rat behaviour and L-DOPA, DA, NE, DOPAC content in rat brain structures was studied depending on the level of the animals' emotional-behavioural reactivity. The results indicate that L-DOPA metabolism in striatum, n. accumbens and hypothalamus in intact animals with high emotional reactivity was the greatest. Administration of Madopar (50 mg/kg) induced significant behavioural disturbances in animals with less emotional-behavioural response patterns. In contrast, 125 mg/kg Madopar completely abolished individual differences in the rats' behaviour and DA, but not L-DOPA and DOPAC content. The correlation between behavioural and biochemical differences in two groups of animals is discussed in view of distinctions in L-DOPA and DA compartmentation process.     

The dose-dependent action of naloxone on systemic and portal circulation in acute blood loss in rats

Using the method of contact luminescent biomicroscopy of the liver and the intestine coupled with the ultrasonic measurement of systemic blood pressure, blood flow velocity in the portal vein and hepatic artery it has been established that in rats with acute decompensatory hemorrhage naloxone increases blood pressure and improves the state of protal macro and microcirculation only after i. v. injection of large dose (5 mg/kg). Naloxone does not influence the dynamics of acute compensatory hemorrhage and the development of the posthemorrhagic microcirculatory disturbances (local microstases, microthromboses, erythrocyte aggregation).     

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

Background  

Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE.     

Glucose-sensing pulmonary delivery of human insulin to the systemic circulation of rats

In an attempt to achieve post-inhalation self-regulated insulin release, we constructed a microparticle agglomerate of nano-sized liposomal particles, with the agglomeration facilitated by cross-linkages capable of cleavage by glucose. The particles exhibited a small aerodynamic diameter within the human respirable range, but a large geometric diameter that prevents macrophage uptake and clearance. Upon intratracheal instillation of the "glucose-sensitive" microparticle into the lungs of rats, hyperglycemic events triggered an acceleration of the release of insulin achieving normoglycemia shortly after "sensing" the elevated systemic glucose. This work is a demonstration of an inhalable particle with long residence times in the lungs capable of modulating insulin release based on systemic glucose levels.     

Malic enzyme response to triiodothyronine in the brain of neonatal rats

Malic enzyme activity in the soluble fraction of the neonatal brain of hypothyroid rats was observed to be lowered as compared to that of the control animals (p less than 0.01). Administration of triiodothyronine to the neonates of control animals resulted in significant enhancement (p less than 0.001) in the activity of the Malic enzyme. Our studies show that brain malic enzyme which is involved in lipogenesis and hence in myelination responds to triiodothyronine in the early stage of life.     

Generation of thioarsenicals is dependent on the enterohepatic circulation in rats

Three minor sulfur-containing arsenic metabolites: monomethylmonothioarsonic acid (MMMTA(V)), dimethylmonothioarsinic acid (DMMTA(V)), and dimethyldithioarsinic acid (DMDTA(V)) were recently found in human and animal urine after exposure to inorganic arsenic. However, it remains unclear how the thioarsenicals are formed in the body and then excreted into the urine. It is hypothesized that the generation of thioarsenicals occurs during enterohepatic circulation. To address this hypothesis, male Sprague Dawley (SD) rats and Eisai hyperbilirubinuric (EHB) rats (with deficiency of multidrug resistance-associated protein 2) were orally administered a single dose of inorganic arsenite (iAs(III)) at 3.0 mg kg(-1) of body weight. Five hours after dosing, less than 1.0% of the dose was recovered in the bile of EHB rats, while more than 27% of the dose was recovered in the bile of SD rats, with the majority being monomethylarsinodiglutathione [MMA(SG)(2)] with a small amount of arsenic triglutathione [iAs(SG)(3)]. During the early time periods (3 h and 6 h) the arsenic levels in the liver, red blood cells (RBCs) and plasma of EHB rats were higher than those of SD rats, and approximately 76% and 87% of the dose was recovered in the RBCs of SD and EHB rats, respectively, at day 5 after dosing. However, there were no significant differences in arsenic concentration in urine between the two types of animal. Regarding the arsenic species in the urine of both types of rat, significant levels of thiolated arsenicals MMMTA(V) and DMMTA(V) were detected in SD rat urine, however in EHB rat urine only low levels of DMMTA(V) were detected. The present result of the metabolic balance and speciation study suggests that the formation of MMMTA(V) and DMMTA(V) in rats is dependent on enterohepatic circulation. In addition, in vitro experiments indicated that arsenicals excreted from bile may be transformed by gastrointestinal microbiota into MMMTA(V) and DMMTA(V), which are then absorbed into the bloodstream and finally excreted into the urine.     

Morphofunctional evaluation of the condition of the brain in rats with different degrees of recovery of neurological status following arrest of systemic blood circulation

The brain status was studied for four days after resuscitation of rats with different degrees of recovery of the neurological status after systemic circulatory arrest induced by the occlusion of vascular bundles of the heart. Morphometric analysis of the population of Purkinje cells from the two different functional zones of the cerebellum revealed that in comparison with completely recovered rats, the animals with disturbed neurological status were characterized by loss of neurons, disturbed composition of the neuronal population, development of severe dystrophic cell changes. The lateral zone of the cerebellum hemisphere was most affected. Four days after resuscitation all the animals showed a sharp increase in the size of the nucleus of Purkinje cells, which is considered to be one of the mechanisms of neuronal adaptation to hypoxia.     

The neonatal glucocorticoid treatment-produced long-term changes of the pituitary-adrenal function and brain corticosteroid receptors in rats.

Two distinct periods of sensitivity to elevated glucocorticoid hormone levels during postnatal development of the pituitary-adrenal axis were studied. Wistar rats were injected subcutaneously (s.c.) with cortisol (1 mg/kg) on postnatal days 1-5 or 14-18. The steroid treatment during the first postnatal week resulted in a decrease of the morning basal and stress-induced plasma corticosterone levels in 30 day-old male rats, as well as in rats that were injected with cortisol on the third postnatal week. Stress-induced corticosterone levels in 90-day old cortisol-treated rats were determined in blood samples drawn from the tail vein before the restraint stress, immediately after the 20-min long stress, then 60 and 180 min afterwards. Only the rats treated with cortisol during the third week showed a prolonged stress-induced corticosterone secretion, with the highest corticosterone level in 180 min after the restraint stress. The early neonatal cortisol treatment had no effect on (3)H-corticosterone binding in all studied brain areas of the 90-day old rats. The rats treated with cortisol at the 14-17th postnatal days showed a significantly lower (3)H-corticosterone binding in the frontal cortex, hippocampus, and hypothalamus. These findings suggest that the third week of life in rats is more sensitive to elevated levels of corticosterone than the first one. The high level of glucocorticoids at this period has long-term effects on the efficiency of the negative feedback mechanisms provided by hypothalamus-pituitary-adrenal axis.     

Regulation of peripheral and systemic blood circulation in rats in conditions of acute nitrite hypoxia

Regulation of the systemic and peripheral hemodynamics in the conditions of acute nitrite hypoxia (doses of NaNO₂ 10, 30, and 50 mg/kg of the body mass) were studied on white male rats. It was shown that NaNO₂ causes a quick dose-dependent decrease in the blood pressure with an intensification of the parasympathetic tonus and development of bradycardia. The hemodynamics was restored as the oxygen capacity of the blood decreased with an increase in the sympathetic tonus and development of tachycardia. The role of intracardial metasympathetic structures and the renin-angiotensin system in cardiovascular adaptation to hypoxia was established. Adaptation to nitrite hypoxia is accomplished by a coordinated interaction of neurogenic and humoral factors. A combination of pharmacological agents, which include separate links of regulator systems of the organism, leads to failure of the adaptation process.     

Changes in the glial condition in different sections of the rat brain after stopping the systemic circulation]

The effect of ischemia on the expression of GFAP in astrocytes of cerebrum, hippocampus and cerebellum was studied on rat clinical death model. Cardiac arrest was induced by 10-or 15-min intrathoracic compression of the heart vascular bundle. Immunohistochemical staining showed that GFAP immunoreactivity significantly increased in the white matter, and GFAP-expressing astrocytes appeared in the gray matter. The reaction activity correlated with ischemia duration and phases of postresuscitation process. The obtained data are indicative of possible changes in the astrocytes condition in the absence of manifest lesions of neurons. This brings up the question of the role of glia homeostasis derangements in the formation of brain postresuscitation pathology.     

Effect of reinfusions of autologous blood on the systemic and portal circulation in acute blood loss in rats

The experiments on rats using the method of contact luminescent biomicroscopy coupled with the ultrasonic measurement of systemic blood pressure and blood flow velocity in the portal vein and hepatic artery have revealed that portal micro- and macrocirculation reflects the degree of efficacy of acute hemorrhage treatment with autoblood. Autoblood infusion in animals with compensatory type of posthemorrhagic period restored systemic blood pressure and blood flow velocity in the portal vein and hepatic artery, promoting the development of erythrocyte aggregation and local microcirculation disturbances in the central zone of hepatic functional elements.     

Myostatin expression is regulated by underfeeding and neonatal programming in rats

Confusing results have been reported regarding the influence of nutritional status on myostatin levels. Some studies indicate that short-term fasting results in increased myostatin mRNA levels in skeletal muscle, evident in several species. In contrast, other studies have demonstrated either a decrease or no change in myostatin levels during fasting. In the present study, we investigated the effect of different patterns of food deprivation on muscle myostatin expression in both newborn and adult rats. Adjustment of litter size in neonatal rats is a well-established model to study the effect of early overfeeding or underfeeding on body composition and in this study resulted in modifications in the pattern of muscle myostatin expression. Rat pups growing in large litters (22–24 newborns) showed a decrease in muscle myostatin mRNA and protein levels at 24 days of age. Interestingly, these effects were maintained at 60 days of age despite rats having free access to food since weaning, thus suggesting that changes in myostatin expression induced by neonatal reduction of food intake are long-lasting. In contrast, no changes in myostatin mRNA levels were observed in adult rats when food intake was decreased during 7 days by either food restriction or central leptin treatment. Similar results were obtained when food restriction was maintained in adult rats for a longer period (7 weeks), despite significant muscle loss. Overall, these data suggest that myostatin gene expression is programmed by nutritional status in neonatal life.