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Axon, in development and injury
Polčanová, Zuzana ; Kárová, Kristýna (advisor) ; Novák, Ondřej (referee)
The cytoskeletal structure of growth cones plays an important role in both the development of the nervous system and during periods of axon re- generation. The growth cone is a highly dynamic structure located at the tip of growing axons, providing navigation and movement. Signalling cascades are activated that lead to the regulation of the growth cone cytoskeleton, defining its displacement, rotation, or collapse. Despite advances in under- standing guidance cues and their mechanisms of action, knowledge of what happens to the nervous system after injury is lacking. Unlike axons in the peripheral nervous system (PNS), that are able to regenerate after neuronal injury, axons in the central nervous system (CNS) loose regenerative ability as they mature. Unravelling the mechanisms of axon guidance, together with their behaviour after axotomy and regeneration, is extremely important for the understanding of CNS injuries and to provide treatment of these injuries in the future.
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Pathophysiology of Spinal Cord Injury Studied by In Vivo Optical Imaging
Vančíková, Sabína ; Valášková, Barbora (advisor) ; Špicarová, Diana (referee)
Patients suffering from spinal cord injury experience physical, social, and vocational impairment. It is a condition often causing a permanent disability mainly due to axonal regeneration incapability in the central nervous system. The primary insult simultaneously damages cells in the lesion site and initiates a cascade of secondary cellular, vascular, and biochemical events extending the injury. These pathophysiological mechanisms are examined using multiple approaches. Novel imaging techniques complement classical histopathological methods and neuroanatomical tracing. Recent studies employ transgenic mice and two-photon microscopy to observe single cells in the injury site and the nearby vasculature in vivo longitudinally. In vivo optical imaging enables studying of axonal responses, such as degeneration, regeneration, and neurovascular interactions. It also gives an opportunity to assess the effects of applied drugs directly. New findings lead to a better understanding of the pathophysiology of spinal cord injury, resulting in the ability to develop other therapeutic strategies improving the outcome after injury. Keywords: spinal cord injury, pathophysiological mechanisms, axonal regeneration, Wallerian degeneration, animal models, transgenic mice, in vivo imaging, two-photon excitation microscopy
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Inhibitors of axonal regeneration and their importance for neuroplasticity, behaviour and memory
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hock, Miroslav (referee)
The central nervous system of higher vertebrates, in contrast to the peripheral one, doesn't regenerate. That is because of the presence of many growth inhibitors produced by a glial scar and oligodendrocytes; the most important inhibitors are MAG (myelin-associated glycoprotein), OMgp (oligodendrocyte-myelin glycoprotein) and mainly Nogo protein. Nogo-A is one of three isoforms of the Nogo protein located primarily in the brain and the spinal cord where it causes the degradation of growth cones, inhibits the growth of neurites, restricts the neuroplasticity and prevents the regeneration of injured axons in adulthood. The Nogo receptor complex serves for a reception of signals and the following signal cascade causes the destabilisation of actin filaments. There are also other receptors for Nogo-A, e. g. the PirB receptor. During the development, Nogo-A is highly expressed by neurons but in adulthood, the main producers are oligodendrocytes. It is noteworthy, that neuronal expression of Nogo-A doesn't decrease after birth in structures with high plasticity, e. g. in the hippocampus which is important especially for spatial learning and memory. In the hippocampus, Nogo-A keeps a balance between the synaptic plasticity and stability and restricts the long-term potentiation. Therefore, this bachelor's thesis...
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