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Genetic determination of cholesterolemia regulation
Vlachová, Miluše ; Kovář, Jan (advisor) ; Vrablík, Michal (referee) ; Kazdová, Ludmila (referee)
Most types of hypercholesterolemia are of polygenic origin. Some genes related to hypercholesterolemia are known, although all genes responsible for cholesterolemia regulation have not been characterised yet. To identify these new genes, animal models with spontaneous defects in cholesterol metabolism could be very useful. Moreover, a number of variations and polymorphisms have been found to influence blood cholesterol levels in humans. Some may also affect cholesterolemia responsiveness to dietary fat. The Prague hereditary hypercholesterolemic (PHHC) rat is a unique model of hypercholesterolemia induced by dietary cholesterol alone (without administration of cholic acid or thyrotoxic drugs). It exhibits modestly increased cholesterolemia when fed chow and responds to a diet containing cholesterol with a several-fold increase of cholesterolemia to concentrations comparable to those observed in hypercholesterolemic patients. Hypercholesterolemia in this model is characterised by accumulation of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) enriched by cholesterol. In an experiment with tyloxapol (an inhibitor of lipoprotein lipase) we found that PHHC rats on a cholesterol diet incorporated twice as much cholesterol into VLDL as Wistar rats, although liver...
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Model of cerebral focal cortical ischemia and its parametrization
Svoboda, Jan ; Otáhal, Jakub (advisor) ; Konopková, Renata (referee)
Title of work: Model of cerebral focal cortical ischemia and its parametrization Work objectives: The aim of this diploma thesis was to apply modified model of focal cortical brain ischemia induced by phototrombosis and subsequently determinate its parameters. Methods: Intravenous application of photosensitive Rose Bengal dye was followed by continual illumination of green laser beam over the left sensorimotocortex for 10 minutes. Following illumination, the dye is activated and produces singlet oxygen that damages components of endothelial cell membranes, with subsequent platelet aggregation and thrombin formation, which eventually determines the interruption of local blood flow. This approach, initially proposed by Rosenblum and El-Sabban in 1977, was later improved by Watson in 1985 in rat brain. For histological evaluation of ischemic brain damage, animals were overdosed with urethane and transcardially perfused. Results: Histological examination of brains showed significant ischemic damage in all experimental animals. Lesion was located in left hemisphere and penetrated thought the grey matter in various extents. Size of lesion, its localization and depth has shown only a small variability in the individual groups. Noticeable differences were found right after comparing experimental groups....
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Curcumin in the treatment of traumatic spinal cord injury
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Martončíková, Marcela (referee)
Spinal cord injury is a very significant clinical as well as social problem with extensive consequences, affecting the patient and also his/her family. Great efforts have been devoted to searching for an effective treatment, which would improve their situation. This thesis evaluated the effects of the natural compound curcumin on spinal cord injury using an experimental balloon compression model. Male Wistar rats were randomized into two groups following the lesion induction, namely vehicle- or curcumin-treated. The behavioral recovery was evaluated using a set of locomotor and sensory tests and a histological and imunohistochemical analysis was performed. The qPCR method was used to observe the expression of some genes related to regeneration and immune response. It was demonstrated that curcumin improved locomotor recovery after the spinal cord injury, particularly in the early stages. Morphometric analysis of the gray and white matter sparing didn't confirm any differences between the two groups. Nevertheless, the glial scar formation was significantly reduced around the central part of the lesion in the curcumin treated group and also the NF-κB activity was substantially inhibited. The gene expression analysis demontrated downregulation of Gfap and Rantes genes and upregulation of the Irf5 gene...
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Influencing motor activity in laboratory rat offspring by specific antagonist of AMPA receptors.
Soukupová, Andrea ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
The IEM 1460 is a potential age-specific anticonvulsant and an indicator of the distribution of AMPA receptor subtypes among rat brain cells. It is a derivative of adamantane, that was tested in previous studies on models of human myoclonic and generalized tonic-clonic seizures with promising results. In this thesis we evaluated its effect on the motor activity of rat offspring in the age of 12, 18 and 25 days, we used 90 animals in total . The effect was evaluated 30 minutes after intraperitoneal administration of IEM 1460 in two doses, 10 mg/kg or 20 mg/kg, and was compared to the control animals with physiological solution applied intraperitoneally in amount of 20 mg/kg. To test the animals we used Open field test, righting reflex, negative geotaxis, horizontal bar test, rope climbing test, regular and irregular horizontal ladder test. The tests were applied to animals in mentioned order. There were found significant changes influencing motor behaviour, primarily in the 12 days old animals with the dose of 20 mg/kg IEM 1460 and in the 25 days old animals with both doses of IEM 1460, 10 and 20 mg/kg. In the 18 days old animals the results were less significant. Powered by TCPDF (www.tcpdf.org)
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Consequences of experimentaly induced perinatal cerebral ischemic lesion
Bahníková, Eva ; Otáhal, Jakub (advisor) ; Konopková, Renata (referee)
1 Abstract Title: Consequences of experimentally induced perinatal cerebral ischemic lesion. Aim: This thesis aims to present the issues and analyze current knowledge in the field of perinatal brain damage, particularly perinatal cerebral ischemic lesions as the most common brain infarction in children. Basic characteristics of the disease, syndromology, pathophysiological mechanisms and risk factors are emphasized. Following the theoretical background the thesis analyzes current trends as well as the limitations of the diagnostics and therapy. The aim is to highlight the need for early diagnosis and emphasize the potential of preventive treatment strategies. The practical part follows the theoretical background and expands the topic on the analysis of motor and behavioral consequences of experimentally induced perinatal ischemic stroke. Method: Cerebral focal ischemia was induced experimentally by photothrombotic method to seven days old rats. Rose Bengal intravenously followed by continual illumination of the senzorimotor cortex using a green laser beam for 10 minutes was induced platelet aggregation and subsequent thrombosis. Eight animals at age of two months were evaluated for 7 days via observational cages PhenoTyper. Results: The theoretical part collected and processed theoretical data on the...
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Circadian regulation of STAT3 protein in the SCN and it's activation by leptin in the SCN, other parts of hypothalamus and the pineal gland
Moníková, Veronika ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
JAK/STAT signaling pathway is one of the most studied intracellular cascades transmitting signals from the extracellular environment to the cell nucleus in order to affect expression of target genes. Circadian clocks localized in the suprachiasmatic nuclei (SCN) of the hypothalamus are sensitive especially to light but they can respond to non-photic stimuli such as growth factors, opioids, leptin and cytokines that have been demonstrated to perform its function via the JAK/STAT signaling pathway. The recent findings of our laboratory demonstrated that STAT3 protein is highly produced by SCN of rat. Primary aim of our experiments was to test the circadian regulation of STAT3 production in SCN and describe the effect of exogenously administered leptin on STAT3 phosphorylation in the SCN, pineal gland and hypothalamic structures responsible for regulated feeding behavior and energy metabolism. Because activation of leptin receptors may stimulate a number of other signaling cascades, we chose phosphorylated forms of kinase ERK1/2 and GSK-3β as other markers of intracellular changes after administration of leptin in the studied structures. Our results proved rhythmic production of STAT3 protein in SCN of rat and indicated circadian regulation of sensitivity to leptin in hypothalamic structures. The data...
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Experimental rat models in traumatic spinal cord injury research
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Mrózková, Petra (referee)
A large number of spinal injuries that cause damage to the spinal cord occur every year. Such damage to spinal cord tissue leads to a number of dysfunctions that significantly reduce quality of life and therefore the development of effective therapies remains a very important issue. The use of animal models is considered the major tool of this research field, enabling the testing of new treatments as well as observing ongoing pathophysiological processes. Rats are the most frequently used animal model due to the many possible ways of creating a spinal cord lesion on them. The contusion model uses a computer-controlled device to simulate the spinal cord contusion and therefore is highly precise. However, a compression model seems to be the most suitable model for pathophysiological studying. Besides contusion it enables persistent compression to the spinal cord. Transection and hemisection methods are intended for axonal regeneration research, as only these models can reliably distinguish new growing fibers from the preserved ones. Less often photochemical and excitotoxic models are used. Lastly, dislocation and distraction of vertebrae or damage to the spinal cord using heat or cold can be carried out. Each of the models have their own unique features that make them optimal to use in different...
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Flexibility in spatial cognition of rat
Staňková, Anna ; Svoboda, Jan (advisor) ; Telenský, Petr (referee)
5 Abstract Cognitive flexibility is an ability to adapt a behavior according to a dynamic changes in an environment. It belongs to executive functions, along with the processes of working memory, attention, motivation and others. Flexibility is important in the process of changing "stimulus-response" contingency at the time when the initial stimulus no longer leads to reward. According to the nature of the changes we can distinguish three types of cognitive flexibility: reversal learning, intradimensional set shifting and extradimensional set shifting. The processes of cognitive flexibility take place in fronto-striato-thalamic circuit with numerous connections to other brain regions, especially the limbic system. Deficit in cognitive flexibility belongs among cognitive symptoms of schizophrenia, a psychiatric illness we studied in the experimental part of this work using its analogue in rat. The aim of the experimental work was to test cognitive flexibility deficit in the rat model of schizophrenia-like behavior in the Carousel maze in four versions of task with different cognitive load. Animal model of schizophrenia was induced by acute administration of non-competitive NMDA receptor antagonist MK-801 at doses of 0.05 and 0.10 mg/kg i.p. Reversal learning was not damaged in this type of task following the...
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Behavioral expression of pain in rats
Zámečník, Jakub ; Vaculín, Šimon (advisor) ; Boukalová, Štěpána (referee)
The aim of this work is to summarize the current knowledge regarding the behavioral expressions of pain in rat. The work is focused on rats, because they are one of the most used laboratory animals, and may experience pain in some experiments. Behavioral expressions of pain were selected, because they are quite easily recognizable and measurable. The reader will be first acquainted with the necessary basics associated with the phenomenon of pain, with its conception in animals, with classification, physiology and for example with the ways in which are in rats experimentally induced pain. Then in the second part, there are shown individual behavioral expressions with examples in which cases were these manifestations observed. So everyone who is interested can learn something about pain in connection with the avoidance reaction, pose, appearance, specific movements of rat, vocalization, changes in eating and drinking, changes in activity, anxiety, cognitive functions and many other expressions. The work can be valuable contribution for all workers with animals and with its character can contribute to animal welfare. Powered by TCPDF (www.tcpdf.org)
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Pathogenesis of hypercholesterolemia in Prague hereditary hypercholesterolemic (PHHC) rat
Rybáková, Kateřina ; Vlachová, Miluše (advisor) ; Poledne, Rudolf (referee)
Hypercholesterolemia represents a major risk factor of cardiovascular disease. A number of experimental models is used for study of hypercholesterolemia pathogenesis and therapy. This thesis concentrates on characterization of one of these models. Prague hereditary hypercholesterolemic (PHHC) rat is such a suitable model for study of hypercholesterolemia. Although the majority of plasma cholesterol is transported by high density lipoprotein in PHHC rat fed standard diet, PHHC rat fed cholesterol diet develops hypercholesterolemia comparable to that of humans. The advantage of this model is that hypercholesterolemia develops without the need for addition of bile acids or other hepatotoxic substances to the diet. The hypercholesterolemia of PHHC rat is caused by slowed down catabolism of cholesterol-rich very low density lipoprotein (VLDL). These cholesterol-rich particles are synthesized in the liver. We found out that PHHC rat fed 1% cholesterol diet accumulates cholesteryl esters (CE) in the liver and also in the VLDL. Acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP) may participate in the increased incorporation CE into VLDL. We found out no difference in ACAT and MTP activities in the liver between PHHC rats and control animals. Neither ACAT activity...
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