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Circadian system as a modulator of neuroinflammation
Kotková, Eliška ; Spišská, Veronika (advisor) ; Dočkal, Tereza (referee)
The circadian system is involved in the regulation of biological rhythms in physiological, behavioural and immune processes. These rhythms can be found in the central nervous system, including the blood-brain barrier, astrocytes, microglia, and the pineal gland, which produces the hormone melatonin. Neuroinflammation is a complex response of the central nervous system to inflammatory stimuli by rhythmic expression of pro-inflammatory and anti-inflammatory mediators or by rhythmic regulation of immune system cells. Studies have examined the influence of genes and proteins of the circadian system, suprachiasmatic nuclei, melatonin, and glial cell rhythms on neuroinflammation. Lipopolysaccharide was used to induce neuroinflammation in these studies. Based on these studies, the effect of melatonin on mikroglia and endothelial cells, and the responses of suprachiasmatic nuclei was evaluted as the most important circadian modulator of neuroinflammation. This thesis describes the basic principles of the circadian system and neuroinflammation, with the last section presenting the modulation of neuroinflammation by the circadian system. Keywords: astrocytes, blood-brain barrier, circadian system, cytokines, immune system, melatonin, microglia, neuroinflammation, suprachiasmatic nuclei
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The role of microglia and astrocytes in Alzheimer's disease
Pospíšilová, Eva ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
Alzheimer's disease is a neurodegenerative disease that affects the central nervous system and is characterized mainly by problems with memory abilities. With the more aging population, the number of patients with this disease is gradually increasing, so Alzheimer's disease research is becoming one of the main priorities of today's health care. Although the research has been going on for more than a century, the exact causes of the Alzheimer's disease are still unclear. For a long time, the main role was attributed to the pathology of amyloid β and tau protein, the basic pathophysiological features of this disease, but in recent years, it has become clear that microglia and astrocytes also play an important role. These glial cells affect the amount of amyloid β and the hyperphosphorylated tau protein, but they are also crucial for maintaining homeostasis of the central nervous system. Activation of microglia and astrocytes in Alzheimer's disease can lead to disruption of the physiological functions of these neuroglia, and thus to problems with the removal of amyloid and tau protein, but also to the induction of chronic neuroinflammation. This work aims to summarize and organize the basic knowledge about the role of microglia and astrocytes in Alzheimer's disease, while focusing mainly on their role...
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Involvement of the neuroimmune system in Alzheimer's disease
Chaloupková, Barbora ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
Alzheimer's disease afflicts more and more people with increasing life expectancy. The causes of this disease are still not fully understood and explained. An effective treatment is still lacking. One of the reasons is a lack of effective biomarkers of the disease in its early stages before the onset of cognitive deficits. Current research focuses on the neuroimmune system. Emerging evidence shows that changes in its function play a significant role in Alzheimer's disease. This bachelor's thesis describes the interaction of components of the neuroimmune system in the preclinical stages and progression of Alzheimer's disease, their use as biomarkers in the diagnosis of preclinical and clinical stages of AD, and subsequently their potential use in the therapeutic treatment of AD. Key words: Alzheimer's disease, neuroimmune system, neuroinflammation, therapeutic treatment, biomarkers
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Mechanisms of neurophatic pain states development
Přibáňová, Tereza ; Mrózková, Petra (advisor) ; Kuchtiak, Viktor (referee)
Pain is a natural warning signal that protects organisms from actual or potential damage. Upon the stimulation (burns, cuts, inflammation) of nerve endings - nociceptors, nerve signals are conducted via the peripheral nerve fibres into the spinal cord and brain, where they are then processed as painful, and a reaction occurs. Neuropathic pain, on the other hand, is pain caused by an injury or disease of the somatosensory system itself. Neuropathic pain has a substantial impact on the patient's quality of life and is likely to become more prevalent as the population grows older and the rates of diabetes and chemotherapy treatments rise. However, the treatment of neuropathic pain is often insufficient and comes with a number of undesirable side effects, which constitute a significant clinical problem. Research leading to the understanding of the molecular mechanisms of the development and maintenance of neuropathic pain is necessary in order to enhance the treatment of these states and to make it more effective. There is a myriad of factors responsible for the development of neuropathic pain, namely mechanisms which maintain the balance between inhibitory and excitatory somatosensory signalling, changes in the amount or composition of receptors and channels at the surface of the neuron, and most...
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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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Neuroinflammation and mechanisms of neuropathic pain development
Kalynovska, Nataliia ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee) ; Hejnová, Lucie (referee)
Neuropathic pain represents a possible outcome of neural tissue injury; it occurs also as a concomitant symptom of different diseases or as a side effect of several treatments. Up to date, it constitutes a great challenge in clinical practice, as currently available treatments are still unsatisfactory. Mechanism-based treatment approaches are promising strategy in neuropathic pain management. However, there is still a lack of information about the exact mechanisms involved in the development and/or maintenance of neuropathic pain. This Doctoral Thesis is aimed to explore the mechanisms underlying the development of neuropathic pain states in different models. The principal part of this work is focused on the study of anti-inflammatory effect of Angiotensin II receptor type 1 (AT1R) blocker, losartan, in two different models of peripheral neuropathy: paclitaxel-induced peripheral neuropathy (PIPN) and spinal nerve ligation (SNL). The work also aimed to access the involvement of spinal transient receptor potential vanilloid type 1 (TRPV1) channels in the process of neuronal activation induced by paclitaxel (PAC) and chemokine CCL2 treatment. In order to fulfil the abovementioned aims, behavioral, immunohistochemical and molecular methods were used. For every model of peripheral neuropathy, the...
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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole ; Javorková, Eliška (advisor) ; Kanderová, Veronika (referee)
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
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The principles of neurosurgical and intensive care liquorology
Kelbich, Petr ; Krejsek, Jan (advisor) ; Krahulík, David (referee) ; Jílek, Petr (referee)
The principles of neurosurgical and neurointensive care liquorology We observed the development of the cerebrospinal fluid (CSF) patterns in 120 patients after bleeding in the CNS (central nervous system). We used our original cytological- energetic principle to investigate 1453 samples of the CSF from these patients. The principal aim of our investigation is the detection of immunocompetitive cells in the CSF and the specification of their activation via the coefficient of energy balance (KEB). Furthermore we evaluated the numbers of erythrocytes and leucocytes in the CSF and also the catalytic activities of the aspartate aminotranspherase (AST) in the CSF as biomarkers of structural disorder of the CNS. Our goal was to evaluate a three week long development of the CSF patterns to gain more accurate information for a more effective therapy and for a better prediction of further clinical development of these patients. We confirmed that following biomarkers were unfavourable for the development of the CSF compartment and probably the CNS as a whole: higher extent of bleeding in the CNS; higher frequency of the neutrophile granulocytes in the CSF compartment; higher extent of anaerobic metabolism in the CSF compartment; higher level of the catalytic activity of the AST in the CSF; higher age...
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