Cardiopulmonary adaptation to chronic hypoxia was compared in rats exposed to simulated high altitude (barochamber, 8 h per day, 5 days a week, stepwise up to 7000 m, a total of 24 exposures) either from the 4th day or the 12th week of postnatal life. Pulmonary hypertension and right ventricular (RV) enlargement were comparable in both age groups. Whereas in young hypoxic animals the individual values of RV weight increased linearly with a rise of RV pressure (r=0.72), no significant correlation was found in adult rats. Chronic hypoxia increased the concentration of cardiac collagenous proteins; this effect was more pronounced in adult animals. On the other hand, the collagen l/lll ratio was markedly lower in young rats suggesting increased synthesis of collagen III in this age group. A protective effect of adaptation, i.e. increased cardiac resistance to acute hypoxic injury, was similar in both age groups and persisted even 4 months after removal of animals from the hypoxic atmosphere.
Animal models are important for the investigation of mechanisms and therapeutic approaches in various human diseases, including schizophrenia. Recently, two neurodevelopmental rat models of this psychosis were developed based upon the use of subunit selective N-methyl-D-aspartate receptor agonists - quinolinic acid (QUIN) and N-acetyl-aspartyl-glutamate (NAAG). The aim of this study was to evaluate pain perception in these models. QUIN or NAAG was infused into lateral cerebral ventricles neonatally. In the adulthood, the pain perception was examined. The rats with neonatal brain lesions did not show any significant differences in acute mechanical nociception and in formalin test compared to controls. However, the neonatally lesioned rats exhibited significantly higher pain thresholds in thermal nociception. Increased levels of mechanical hyperalgesia, accompanying the sciatic nerve constriction (neuropathic pain), were also observed in lesioned rats. Although hyperalgesia was more pronounced in QUIN-treated animals, the number of c-Fos-immunoreactive neurons of the lumbar spinal cord was similar in experimental and control rats. We conclude that neonatal brain lesions attenuated the thermal perception in both nociceptive and neuropathic pain whereas mechanical pain was increased in the model of neuropathic pain only. Thus, nociceptive and neuropathic pain belongs - in addition to behavioral changes - among the parameters which are affected in described animal models of schizophrenia., M. Franěk ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.
We tested the effect of perinatal (one week prenatal and one week postnatal) normobaric hypoxia on the immune response of rats in their 9th week of life. We found that perinatally hypoxic rats produced less serum antibodies after sequential immunization with ovalbumin and sheep red blood cells. Also phagocytosis of HEMA microparticles by neutrophil leukocytes from perinatally hypoxic rats was depressed as well as the oxidative burst of their peritoneal macrophages and neutrophils. These results demonstrate that perinatal hypoxia has an important effect on the immune system of the rat.
Adult rats born in hypoxia but raised in air are more reactive to acute hypoxic challenges. The relation between perfusion pressure and perfusion flow (P/Q plot) was analyzed in the preparation of ventilated perfused lungs isolated from 3 groups of adult rats. Control animals of the first group were born and lived in air, the second group was born in hypoxic chamber and then the rats were raised in air. Rats of the third group were bom in air and exposed to hypoxia in adulthood. The P/Q plot in rats born in hypoxia had lower slope than that in controls. Acute hypoxia in control group resulted in parallel shift of P/Q line to higher pressures. In rats born in hypoxia, however, both intercept with pressure axis and slope were increased. This may be explained by the participation of both collapsible and non-collapsible parts of pulmonary vascular bed in hypoxic pulmonary vasoconstriction. Analysis of distribution of pulmonary vascular resistances by the double occlusion technique confirmed this possibility. In rats born in hypoxia both arterial and middle vascular segment resistances increased during acute hypoxic challenge. In control rats, however, the increase in resistance was restricted to the middle segment only.
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., I. Ošťádalová, A. Babický., and Obsahuje seznam literatury
The effects of chronic diazepam treatment (10 mg/kg/day for 180 days) on the fractional distribution and fatty acid composition of heart phospholipids were studied in male Wistar rats. It was found that diazepam treatment increased the content of phosphatidylcholine and cardiolipin in the heart and slightly increased its phosphatidylcholine fraction. There were no significant changes in fatty acid composition after diazepam treatment in heart phospholipids, with the exception of significant decrease of 20:3n-6 and 20:5n-3 fatty acids. Our findings suggest that diazepam, probably through peripheral benzodiazepine binding sites, altered the content of heart cardiolipin and caused changes in the flux of oxidative phosphorylation in the heart.
The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7- (hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electroencephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats., E. Szczurowska, P. Mareš., and Obsahuje seznam literatury
An increase in bone blood flow (BBF) was observed in rats after castration whereas a decrease in BBF occurred after oestradiol or testosterone. The possible participation of prostaglandins in these changes was demonstrated. The present results show that the endothelium-derived relaxing factor, i. e. nitric oxide (EDRF-NO), might play a role in these hormonal actions on BBF. Until now, almost nothing is known about the possible action of NO on bone circulation. Methylene blue (MB) as a substance blocking EDRF-NO was administered to sham-operated or oophorectomized (OOX) female rats. We determined local blood flow (85Sr-microsphere uptake), cardiac output, blood pressure, heart rate, density of the tibia and ash weight, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. The administration of MB (0.5 % in the food for 4 weeks) significantly lowered both 85Sr- microsphere uptake and blood flow values in the tibia and distal femur of sham-operated and OOX rats. MB lowered cardiac output and blood pressure to the same extent, indicating no change in the vascular resistance. After the administration of MB (0.1 % in the food), 85Sr-microsphere uptake decreased significantly in the tibia of OOX females while no significant change was found in soft tissues. Bone density and ash weight were significantly lower in OOX rats and in sham-operated rats after MB treatment. Finally, the 24-h incorporation of both 45Ca and 3H-proline decreased significantly in OOX females after MB administration (0.04 % in the food). It can be concluded that 1) MB lowers BBF, suggesting the participation of EDRF-NO in BBF regulation, 2) MB does not influence or may even suppress cardiac output and blood pressure in high dosage, 3) MB lowers 24-hour incorporation of 45Ca and 3H-proline into the tibia of OOX rats, which is in agreement with the circulatory effect, 4) MB lowers bone density and ash weight of the tibia in non-castrated female rats. The effects of MB observed in our experiments partially differ from those of arginine-derived blocking agents. This requires further elucidation.
In the central nervous system (CNS), monocarboxylate transporter 1 (MCT1) is expressed in astrocytes and endothelial cells but also in oligodendroglia. Oligodendroglia support neurons and axons through lactate transportation by MCT1. Limited information is available on the MCT1 expression changes in candidate cells in the developing rat brain, especially in corpus callosum which is the most vulnerable area in demyelinating diseases. In the present study, we investigated the expression pattern of MCT1 during postnatal development in the rat corpus callosum using immunofluorescene staining, Western blotting analysis and RT-PCR. We reported that MCT1 gene and protein were consistently expressed in the rat corpus callosum from birth to adult. MCT1/CNPase and MCT1/GFAP immunofluorescence staining demonstrated that most of MCT1 positive cells were co-labeled with cyclic nucleotide 3′ phosphodiesterase (CNPase) in rat corpus callosum from P7 to adult, whereas MCT1+/GFAP+ cells preserve the dominate position before P7. Moreover, there were significant associations between the expression of MCT1 protein and the expression of myelin basic protein (MBP) (correlation coefficient: r=0.962, P=0.009) from P7 to adult. Similarly, the MCT1 mRNA expression was also significantly associated with MBP mRNA expression (r=0.976, P=0.005). Our results are proposing that in the developing brain white matter, MCT1 is predominately expressed in oligodendrocyte though it mainly expressed in astrocyte in early postnatal, which indicate that MCT1 may involve in the oligodendrocyte development and myelination., F. Dong, Y. Liu, Z. Zhang, R. Guo, L. Ma, X. Qu, H. Yu, H. Fan, R. Yao., and Obsahuje bibliografii