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New biomarkers for prognostication after cardiac arrest
Vondráková, Dagmar ; Málek, Filip (advisor) ; Vízek, Martin (referee) ; Rokyta, Richard (referee)
Cardiac arrest is an extremely serious condition characterized by global ischemia followed by reperfusion after successful resuscitation and restoration of spontaneous circulation. Despite all advances in current medicine, the prognosis of cardiac arrest survivors remains very poor. One of the major problems in these patients is, therefore, the early and reliable determination of the prognosis that is necessary for choosing the most appropriate diagnostic and therapeutic approach. However, the current possibilities for early prognostication in cardiac arrest survivors remain very limited. The aims of our work were: (i) to study the possibilities of influencing oxidative stress as one of the key pathogenic factors involved in the development of so-called post-cardiac arrest syndrome; and (ii) to determine the prognostic value of copeptin, neuron-specific enolase (NSE) and markers of oxidative stress in cardiac arrest survivors. In the experimental part of the work we used porcine model of cardiac arrest for the comparison of the effects of hypothermia, ischemic postconditioning (IPC) and administration of nitric oxide (NO) on oxidative stress burden and organ damage; we found that neither NO nor IPC did have a superior protective effect over hypothermia. In the clinical part we have in several...
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Eye Movement Metrics in the Differentiation of Parkinsonian Syndromes.
Bonnet, Cecilia ; Růžička, Evžen (advisor) ; Rokyta, Richard (referee) ; Jeřábek, Jaroslav (referee)
Eye Movement Metrics in the Differentiation of Parkinsonian Syndromes Cecilia Bonnet, MD Summary of thesis submitted for the degree of Ph.D., Charles University, Prague 2017 In this thesis we investigated conjugate and dis-conjugate eye movements (EM) in Parkinson's disease (PD) and other parkinsonian syndromes aiming to characterize and differentiate some aspects of their oculomotricity using infrared video-oculography. First of all we published a practical review for medical students and clinicians describing clinical examination of eye movements, and interpretation of principal findings. Then we examined principal saccadic eye movements and smooth pursuit in the horizontal and vertical directions with video-oculography in a large group of healthy subjects, aiming to help new oculomotor laboratories in the constitution of their own norms. We conclude that age influence EM metrics but not gender or education level. The latency of saccades and the error rate of antisaccaes increases, while the velocity and gain diminishes with age. Saccades should be investigated in the horizontal and vertical plane because they are influenced by the direction of the target, resulting in a right/left and up/down asymmetry. In a third project we focused on a frequent complain of PD patients, namely blurred near vision and...
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Spatial memory in humans and its disorders: From animal models towards schizophrenia
Fajnerová, Iveta ; Vlček, Kamil (advisor) ; Rokyta, Richard (referee) ; Jiruška, Přemysl (referee)
Spatial memory is often studied using spatial tasks originally developed for animals, such as the Morris water maze and the Carousel maze tasks. Both tasks have an important role in the process of identification of brain areas crucial for spatial memory, and also in pharmacological research of animal models of neuropsychiatric diseases. In recent years considerable attention has been devoted to the research and treatment of cognitive impairment in schizophrenia. Comparative research addressing cognitive abilities of both animals and patients in similar tasks, could therefore lead to verification of the predictive and face validity of animal models of this complex disorder. The aim of this study was to create virtual analogues of these tasks, which would allow this comparative approach. This thesis first describes the experiment testing the performance of an animal model of schizophrenia induced by the application of dizocilpine (MK-801) in reversal version of both mentioned spatial tasks, in order to assess mental flexibility and learning abilities affected in schizophrenia. Other two experiments present the findings of the two virtual analogues tested in the first episode of schizophrenia patients. Our results confirm the presence of deficits in spatial memory and mental flexibility, functions dependent on...
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Mild therapeutical hypothermia and oxidative stress after cardiac arrest
Krüger, Andreas ; Ošťádal, Petr (advisor) ; Vízek, Martin (referee) ; Rokyta, Richard (referee)
Successfull cardiopulmonary resuscitation is an essential life-saving tool; nevertheless, general ischemia during cardiac arrest may trigger different pathways that could turn even into a fatal damage; this condition is called post-cardiac arrest syndrome. It has been repeatedly shown that oxidative stress (OS) plays one of the key roles in the development of ischemia-reperfusion injury. However, current evidence on the possible participation of OS in the pathogenesis of post-cardiac arrest syndrome is insufficient. We tested following hypotheses: (i) ischaemia-reperfusion injury after cardiac arrest is accompanied by OS and (ii) mild therapeutical hypothermia decreases OS cardiac arrest. In the experimental part of our work we studied the effects of hypothermia and normothermia on hemodynamic parameters, markers of organ damage and on the OS burden in porcine model of cardiac arrest. Furthermore, we compared the effects of hypothermia with ischaemic postconditioning and nitric oxide administration in the porcine model of extracorporeal cardiopulmonary resuscitation. We found protective effects of hypothermia on all major endpoints including OS in comparison with normothermia; moreover, hypothermia improved also selected variables compared to ischemic postconditioning and nitric oxide. In the...
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The role of charged residues in the activation and modulation of the TRPA1 ion channel
Zímová, Lucie ; Vlachová, Viktorie (advisor) ; Doležal, Vladimír (referee) ; Rokyta, Richard (referee)
Important receptor for sensing painful stimuli is ion channel TRPA1, which is expressed in peripheral endings of nociceptive neurons, where it serves as transducer of physical and chemical environmental signals to the language of the nervous system. The effort to understand the mechanisms of its activity on a molecular level is driven by the vision of progress in treatment of chronic pain in humans. Our work focused on C-terminal cytoplasmic domain of TRPA1 receptor, where we described i.a. the probable binding site for calcium, which is the most important TRPA1 modulator. Using the combination of homology modeling and molecular dynamic simulations with electrophysiological measurements we were able to explain molecular basis of familial pain syndrome caused by TRPA1 point mutation. We contributed to the understanding of the TRPA1 voltage-dependent activation mechanism by describing the amino acids in proximal C-terminus and in S4-S5 linker of transmembrane domain that are directly involved in voltage-dependent gating. Powered by TCPDF (www.tcpdf.org)
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Developmental changes in expression levels of the chosen subunits of NMDA and AMPA receptors and action of their antagonists on physiological and epileptic phenomena
Szczurowska, Ewa Katarzyna ; Mareš, Pavel (advisor) ; Rokyta, Richard (referee) ; Bendová, Zdeňka (referee)
During early stages of postnatal development, glutamate receptors of NMDA and AMPA type, undergo intensive functional changes due to modifications of their subunit composition (Pachernegg et al., 2012: Paoletti et al., 2013). The NR2B-containing NMDARs (NR2B/NMDARs) and GluA2-lacking AMPARs (Ca 2+ -permeable) that are highly expressed in immature brain, are implicated in increased excitability, seizures generation, excitotoxicity, and neuronal death (Vizi et al., 2013). Pharmacological blockade of these types of receptors by their specific antagonists, can exhibit anticonvulsant effects at early stages of postnatal development. Therefore, we tested the influence of the IEM1460, a specific antagonist of Ca 2+ -permeable AMPARs and the Ro 25-6981 maleate, a highly selective and activity-dependent antagonist of NR2B/NMDARs on physiological excitability and epileptic phenomena induced in immature rats. Anticonvulsant action of IEM1460 was tested in two models of epileptic seizures: pentylenetetrazol (PTZ)- induced convulsions and cortical afterdischarges (ADs), induced in animals at P12, P18 and P25. Our results indicate that the effects of IEM1460 on various types of seizures depend on their sites of origin in the brain, developmental stage, and GluA2 subunit expression profile. To clarify the action...
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Utilization of biocompatible hydrogels based on 2-hydroxyethylmethacrylate to bridge the spinal cord lesion
Lesný, Petr ; Syková, Eva (advisor) ; Rokyta, Richard (referee) ; Hampl, Aleš (referee)
Utilization of biocompatible hydrogels based on 2-hydroxyethylmethacrylate to bridge the spinal cord lesion MUDr. Petr Lesný Biocompatible hydrogels based on copolymers of 2-hydroxyethylmethacrylate are suitable for implantation into a central nervous tissue lesion. Our prepared hydrogels were macroporous with predominantly communicating pores, and their mechanical properties were similar to those of spinal cord tissue. After we confirmed their biocompatibility by the growth of mesenchymal stem cells and determined the hydrogel diffusion properties, we implanted the prepared hydrogels into acute spinal cord injury in laboratory rats and studied the process of spinal cord tissue regeneration within the implants. When the hydrogels were implanted in subacute phase of spinal cord injury, we observed favorable impact on the spinal cord tissue regeneration and reduction of pseudocyst formation. Using histological and immunohistochemical methods, we observed the ingrowth of central nervous tissue elements (connective tissue, vessels, neurofilaments, Schwann cells, astrocyte processes) into the hydrogels implanted into the spinal cord hemisections. We have found that copolymerization with a positively charged ammonium salt increases the adhesion of the cells to the hydrogels in vitro and the ingrowth of...
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Obstetric brachial plexus palsy
Mencl, Libor ; Haninec, Pavel (advisor) ; Rokyta, Richard (referee) ; Ehler, Edvard (referee)
Obstetrical brachial plexus palsy (OBPP) displays a stable incidence of 0.15 - 3 per 1,000 live births. Most children show good spontaneous recovery, but a recent literature reviews show that a residual deficit remains in 20% to 30% of children. Shoulder dystocia, macrosomia and instrument delivery, forceps or vacuum extraction present the greatest risk for brachial plexus injury. Caesarean section, having a twin or multiple birth mates seems to offer some protection against injury. The resulting nerve injury may vary from neurapraxia or axonotmesis to neurotmesis and root avulsion from spinal cord. In neurapraxia or axonotmetic lesions complete recovery will usually occur over the course of weeks or months. In a neurotmetic injury or in case of root avulsion, the most sever type of lesion, useful regeneration of axons cannot take place. Although we perform electromyography and imaging studies, the final decision of operation relies heavily on the clinical examination. Manual muscle testing system although reliable for examination of motor power in adults is not suited for use with infants. All patients involved in the study were evaluated using the Active Movement Scale (AMS), which greatly increases the ability to detect partial movements. The results of neurophysiological investigations in older...
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Changes of the eExtracellular space diffusion parameters during acute pathological states in the rodent brain and the role of AQP4 channels in cell swelling
Dmytrenko, Lesia ; Vargová, Lýdia (advisor) ; Druga, Rastislav (referee) ; Rokyta, Richard (referee)
1. SUMMARY The diffusion properties of the extracellular space (ECS), which govern the movement of neuroactive substances through its volume and thus extrasynaptic transmission, are profoundly affected in states associated with cell swelling. In this work we compared ECS diffusion parameter changes during acute cell swelling in vivo in models of pilocarpine-induced status epilepticus (SE) and ischemia/anoxia evoked by cardiac arrest. To elucidate mechanisms involving the aquaporin 4 (AQP4) water channel in pathological cell swelling, we used models of hypotonic stress and elevated K+ in coronal slices of genetically modified mice. The ECS diffusion parameters volume fraction ( = ECS volume/total tissue volume), tortuosity factor (2 = apparent diffusion coefficient/free diffusion coefficient) and non-specific uptake (k') were determined by the real-time iontophoretic method, which was the primary method used in my thesis work. Changes in the activity-related extracellular K+ concentration ([K+ ]e) were measured using ion-selective microelectrodes. The apparent diffusion coefficient of water (ADCW) was determined by diffusion-weighted MRI. In both models in vivo, ECS volume fraction and ADCW decreased; these changes were more profound and their time course was faster during terminal ischemia/anoxia in...
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš ; Stuchlík, Aleš (advisor) ; Zach, Petr (referee) ; Rokyta, Richard (referee)
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention. Powered by TCPDF (www.tcpdf.org)
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