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Age related changes in the central auditory system in the laboratory rat
Burianová, Jana ; Popelář, Jiří (advisor) ; Stuchlík, Aleš (referee) ; Rokyta, Richard (referee)
Age-related hearing loss, presbyacusis, is becoming one of the most common health disabilities in elderly people. Despite intensive research, age-related changes are still poorly understood and, given the continuous aging of the population, it is desirable to improve our knowledge of the mechanisms of presbyacusis. Consequently we decided to study age-related changes that appear in the structure and function of the central auditory system in the brain of experimental animals. In the first experiment we tested the hypothesis that during aging there is substantial decline of GABA-mediated inhibition in the central auditory system of the rat. We evaluated levels of both isoforms of glutamatedecarboxylase (GAD65, GAD67), a key enzyme in GABA synthesis. Western blot analysis revealed an overall decrease in levels of both isoforms in the inferior colliculus as well as the auditory cortex in aged rats. The same pattern was found when we used immunohistochemistry analysis; there was a decrease in the number of GAD65 and GAD67-ir neuronal bodies and a decrease in the density of the labeling. The results were similar for both GAD isoforms and both studied strains - the normally aging Long Evans strain (LE) and the Fischer 344 (F344) strain known for accelerated aging. In the next experiment we evaluated...
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Muscarinic acetylcholine transmission and Alzheimer's disease
Janíčková, Helena ; Doležal, Vladimír (advisor) ; Blahoš, Jaroslav (referee) ; Rokyta, Richard (referee)
Impairment of the cholinergic neurotransmission system is regularly detected in animal models of Alzheimer's disease as well as in human patients suffering from this serious disease. Moreover, there is increasing amount of evidence suggesting that activation of individual mAChR subtypes specifically influences the cleavage of APP, the precursor for β-amyloid. APP can be processed in an amyloidogenic or non-amyloidogenic pathway and a relative abundance of these patways contributes to establishing the final concentration of neurotoxic β-amyloid in the brain. In this work, I have studied the acute and chronic effects of A β1-42 on binding and functional characteristics of mAChR. I have demonstrated that Aβ1-42 present in cell culture expressing the individual subtypes of mAChR negatively and specifically influences the function of the M1 mAChR subtype. I have also detected a decline in muscarinic receptor-mediated signal transduction in brain tissue of young adult APPswe/PS1dE9 mice, a commonly used animal model of Alzheimer's disease. Demonstration of the impairment of muscarinic transmissin in transgenic mice by soluble β-amyloid that occurs earlier than amyloid pathology and behavioral deficit, and its imitation by soluble Aβ1-42 in vitro lend strong support to the notion of the early involvement...
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Astrocytic changes in a mouse model of Alzheimer's disease
Kulijewicz-Nawrot, Magdalena ; Syková, Eva (advisor) ; Rokyta, Richard (referee) ; Zach, Petr (referee)
1. SUMMARY: In this thesis we reported astrocytic atrophy characterized by a reduction in the surface area and volume of GFAP-positive glial cells in the prefrontal cortex of 3xTg-AD mice - an important morphological alteration starting far before any well known histopathological hallmark of AD. This change is present in parallel with homeostatic failure suggested by the decreased expression of GS. Those alterations can have drastic effects on brain connectivity and the biochemistry of the main neurotransmitters within the brain, such as glutamate and GABA. GFAP is implicated in a variety of processes, such as cell migration and proliferation, neurite outgrowth, astrocytic glutamate transporter expression (GLAST and GLT-1) and synaptic plasticity, so that every change can shift the astrocytes' role from physiology to pathology. In the case of affected GFAP-IR astrocytes, the withdrawal of processes from neurons and synapses can lead to a severe transmission crush, due to the uncontrolled spillover of the neurotransmitter from the synaptic cleft, inadequate metabolic support and the lack of a physiological barrier between the affected synapse and other synapses in its close vicinity. This will directly disturb the reciprocal connections between the affected brain regions, inluding the important structures...
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The coronary atherosclerosis regression during hypolipidemic therapy
Kovárník, Tomáš ; Aschermann, Michael (advisor) ; Rokyta, Richard (referee) ; Pudil, Radek (referee)
Background: There is no study focusing on changes of coronary atherosclerosis during dual hypolipidemic therapy with statin and ezetimibe. Methods: 107 patients with stable angina were enrolled and the final analysis was performed in 89 patients. Randomization was 1:1 to the group A (atorvastatin 80mg and ezetimibe 10mg) and to the standard group S. Treatment period was 12 months. Results: Changes of percent atheroma volume (PAV) were -0,4% in group A and + 1,4% in group S, p=0,014. Combine atherosclerosis regression (increase of lumen volume together with decrease of PAV) was found more frequent in group A (40,5%) than the group S (14,9%), p=0,007. The target LDLc level < 2mmol/l, presence of at least four of five atherosclerotic risk factors, and decrease of VCAM level were independent predictors for plaque regression. There were no significant differences in plaque composition between the two groups over the duration of the study. However during analysis the two groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusion: The dual hypolipidemic therapy starts atherosclerosis regression. Despite significant decrease of lipid levels the continuous plaque shift from fibro and fibro-fatty to necrotic with calcification...
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Neuromodulation in treatment of selected dystonic syndromes
Havránková, Petra ; Jech, Robert (advisor) ; Štětkářová, Ivana (referee) ; Rokyta, Richard (referee)
Dystonia is a neurological syndrome characterized by the involuntary contraction of opposing muscles, causing twisting movements or abnormal postures (modified by Fahn, 1987). Writer's cramp is the most common form of task-specific focal dystonia. In the first study, patients with writer's cramp were evaluated for differences in cortical activation during movements likely to induce cramps (complex movements) and movements which rarely lead to dystonia (simple movements). Although complex patient movements during fMRI were never associated with dystonic cramps, they exhibited abnormally decreased cortical activity. This was not observed in simple movements and was unrelated to the character of handwriting or the presence/absence of visual feedback. Our results support the theory of dualistic sensorimotor system behavior in writer's cramp. As the somatosensory system is believed to be affected in focal dystonia, we focused on modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in the second study, in order to improve writer's cramp. In conclusion, 1 Hz rTMS of the SI cortex can improve manifestations of writer's cramp while increasing cortical activity in both hemispheres. Handwriting as well as subjective assessment improved in most...
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Spatial behavior of the rat in non-stationary environments:role of the posterior parietal cortex
Svoboda, Jan ; Stuchlík, Aleš (advisor) ; Hort, Jakub (referee) ; Rokyta, Richard (referee)
Better understanding of cognitive functions and their underlying neural substrate requires appropriate behavioral testing methods. Studying spatial cognition of rat has taken advantage from plethora of tests examining spatial capabilities in stationary environments. However, an animal obviously daily faces situations in which it must response to ever changing elements in its environment. Thus this thesis was aimed to contribute to understanding how an animal represent these non-stationary environments and to elucidating of the role of some brain structures such as posterior parietal cortex or hippocampus.
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Neuroregeneration after spinal cord injury and in amyotrophic lateral sclerosis -possibilities for stem cell therapy
Forostyak, Serhiy ; Syková, Eva (advisor) ; Rokyta, Richard (referee) ; Mazanec, Radim (referee)
Adipose-derived MSC could be used as an alternative for bone marrow MSC in the treatment of acute SCI. We used the intraspinal grafting of rat adipose-derived naïve and predifferentiated MSC to improve motor function after a balloon-induced compression lesion of the rat spinal cord. Grafted cells survived for seven weeks after transplantation, improved motor activity and integrated into the host tissue. They expressed the oligodenrocyte precursor marker NG2 and, occasionally, the astrocytic marker GFAP, but did not transdifferentiate into a neuronal phenotype. Bone marrow MSC may change the disease course and extend lifespan in a rat model of ALS. Combined intraspinal and intravenous transplantation of rat BMSC was performed in symptomatic rats overexpressing the SOD1 G93A gene. Cell-treated animals lived longer compared with sham-treated rats and displayed significantly improved motor activity and grip strength. Rat BMSC survived until the end stage of the disease and were migrating along the white matter of the spinal cord. Grafted cells increased the number of host cells displaying positive staining for neurofilaments and significantly increased the number and also the size of the remaining spinal motoneurons 10-11 weeks after delivery, compared with vehicle-injection. The defragmentation of DNA, a sign...
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Radial approach to coronary catheterizations and interventions
Bernat, Ivo ; Rokyta, Richard (advisor) ; Vojáček, Jan (referee) ; Ošťádal, Petr (referee)
Radial approach in coronary catheterizations and interventions has been only an alternative of the femoral approach. But due to some important advantages radial approach has a chance to become the first choice in majority of catheterized patients. The most important advantage is the reduction of vascular access site bleeding complications. Additonal benefits are patient satisfaction, cost reduction, shorter hospital stay and possibility of the same-day discharge catheterizations and interventions. The aim of our work was to try to answer three open questions: 1. is it possible to catheterize majority of our patients from the left radial artery when 90% of them are right-handed ? 2. what is the optimal care for the radial artery after the procedure in prevention and treatment of radial artery occlusion? 3. is it effective to implement radial approach in primary PCI as a first approach for STEMI patients? The first part relates the left radial approach. After construction of our special variable support for the left arm and forearm we succesfully used this approach in our studies in almost 90% of patients. The second part of this work contains our randomized trial comparing two different doses of unfractionated heparin in prevention of radial artery occlusion after diagnostic cardiac catheterizations....
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The therapeutical effect of rTMS on symptomatology in schizophrenia
Baláková, Lucie ; Horáček, Jiří (advisor) ; Rokyta, Richard (referee) ; Anders, Martin (referee)
The RTMS is a new noninvasive method has the potential to both therapeutic and experimental level. The research presented in this work was dedicated to the application of repetitive transcranial magnetic stimulation (rTMS) in psychiatry. We focused also on a deeper understanding of the mechanisms of action using methods of functional imaging methods and sensing electrical activity of the brain. The experimental part of the research include the testing of cognitive function and their potential effects by stimulating the cerebral cortex district, which is regarded as the seat of that particular modality. We discuss neurobiological factors that may explain the ineffectiveness of therapy and other options are designed to test the use of rTMS in this indication. This is the Reversible stimulation (right) or bilateral stimulation, rTMS targeting the coil at the bottom of the parietal cortex, extending the total period of stimulation and the use of individual navigation based on EEG or functional imaging.
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