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Treatment of spinal cord injury targetting secondary mechanisms
Valášková, Barbora ; Jendelová, Pavla (advisor) ; Hájek, Milan (referee) ; Rokyta, Richard (referee)
1 Abstract Traumatic spinal cord injury (SCI) is severe condition with devastating long- lasting consequences. There is still no available treatment. After initialing mechanical trauma, there is a huge cascade of secondary reactions which amplifies the damage. This thesis is focused on potential therapeutic effect of photobiomodulation, natural anti- inflammatory compounds epigallocatechin-3-gallate (EGCG), curcumin, their combination and extrapure synthetic form of curcumin called "nanocurcumin" on impacts of experimental model of SCI in rats. Photobiomodulation using combination of two synchronized wavelengths 808 and 905 nm improved functional recovery after SCI evaluated by battery of locomotor tests and somatosensory plantar test. The group treated by photobiomodulation obtain better results in all tests. The histopathological analysis showed a positive effect on white and gray matter sparing and our data suggests an upregulation of M2 microglia/macrophages in photobiomodulation treated rats assessed by immunohistochemical and RT-qPCR analysis. Our results demonstrated that the photobiomodulation is a promising non-invasive therapy for improving functional recovery and tissue sparing after SCI. EGCG and curcumin are natural compounds known in Chinese medicine for centuries. Their neuroprotective and...
Possibilities of organ protection after global ischemia during cardiac arrest.
Mudrochová, Hana ; Ošťádal, Petr (advisor) ; Rokyta, Richard (referee) ; Malý, Jiří (referee)
Successful cardiopulmonary resuscitation is the first step to rescue life during cardiac arrest. High mortality even after successful restoration of spontaneous circulation is substantially caused by patophysiological process associated with ischemia-reperfusion injury and it is widely called post-cardiac arrest syndrome (PCAS). There are many patophysiological mechanisms involved in the development and progress of this syndrom; the key role seems to play oxidative stress, triggering the activation cascade of systemic inflammatory reaction. In our study we have tested different possibilities of influencing the post-cardiac arrest syndrom. In the first experimental study we have compared the effect of mild therapeutic hypothermia with controlled normothermia on PCAS in a porcine model of cardiac arrest. In the second study we have compared in the same model the protective effects of mild therapeutic hypothermia, administration of nitric oxide and ischemic postconditioning. Results of the first experiment have revealed that mild therapeutic hypotermia is superior in the resuscitability, maintenance of blood pressure, oxidative stress suppression and organ damage protection than controlled normothermia. In the second experiment we have shown that neither nitric oxide administration, nor ischemic...
Impairment of rat hippocampus after irradiation with leksell gamma knife and evoked proliferation in gyrus dentatus of the adult rat
Náměstková, Kateřina ; Syková, Eva (advisor) ; Druga, Rastislav (referee) ; Rokyta, Richard (referee)
The hippocampus is a brain structure that has been extensively studied in the context of learning and memory has been considered to be involved in processing of emotion as part of the limbic system. This organ was initially connected with the sense of smell and around 1900 the role of the hippocampus in memory was noted by Vladimir Bechterev. The significance of this structure for processing of memory was revealed after William Scoville and Brenda Millner released a report in 1957 about their 10 patients who showed impaired short-term memory after bilateral lesions to the medial temporal lobe, including the hippocampus. This form of surgery was introduced in 1954 to treat pharmacoresistant epilepsy, psychosis, and depression with therapeutic success. The severity of the mainly anterograde amnesia was related to the size of the removed medial temporal lobe portion (Scoville and Millner 1957). The most radical surgery was performed on the patient H.M., who has been seen by more than hundred investigators until today (Corkin 2002). Fig. Powered by TCPDF (www.tcpdf.org)
Tissue microcirculation in cardiac arrest setting - impact of various methods of circulatory support
Krupičková, Petra ; Bělohlávek, Jan (advisor) ; Widimský, Jiří (referee) ; Rokyta, Richard (referee)
Introduction: This dissertation thesis aims to describe microcirculatory changes in cardiac arrest setting and to assess the impact of circulatory supports (i.e. mechanical chest compressions and extracorporeal membrane oxygenation (ECMO)) on tissue microcirculation. Methods and results: Two separate studies were designed. Microcirculation was monitored sublingually by a recent Sidestream Dark Field (SDF) technique and its parameters were evaluated offline, separately for small (of diameter ≤ 20µm) and other vessels. In order to monitor microcirculation during cardiac arrest (CA) and resuscitation (CPR) an experimental pig model was used; eighteen pigs were commenced to 3 minutes of untreated CA and subsequent 5 minutes of mechanical CPR. During CA the microcirculatory parameters deteriorated, in CPR they improved and reached 59 - 85 % of the prearrest values. The microcirculatory variables correlated neither to parameters of systemic circulation (mean arterial blood pressure and carotid blood flow) nor to lactate. In the second, clinical, study the sublingual microcirculation was monitored 29 (± 17) hours after the CA onset in 15 patients, who were after unsuccessful conventional CPR rescued by ECMO. In comparison to healthy (sex and age matched) volunteers, the patients showed mild but...
Secondary prevention practice and prognosis of patients after ischemic stroke
Vaněk, Jiří ; Mayer, Otto (advisor) ; Rokyta, Richard (referee) ; Vítovec, Jiří (referee)
SECONDARY PREVENTION PRACTICE AND PROGNOSIS OF PATIENTS AFTER ISCHEMIC STROKE JIŘÍ VANĚK, M.D. 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic ABSTRACT It is evident that cerebrovascular disease including ischemic stroke belongs to the most common cause of disability or death in the world population. Secondary prevention in poststroke patiens can lead to reduce risk of recurrence or extend lifetime like in coronary heart disease (CHD). The principles of secondary prevention are well implemented in population with CHD, but the situation in poststroke patients is quite different. The assesment of secondary prevention in poststroke patiens and a comparison with patient with CHD was selected for a goal of this study. The study population consisted of Czech patients examined in the framework of well-defined surveys in patients after their first ischemic stroke. Patients represented pooled Czech samples of the project EUROASPIRE Stroke Modul or Stroke Survey in 2007 and in 2013. Better results in acute care were detected. Admissions in stroke unit in 2013 were realized more often than 2007 and fibrinolisis was aplicated more frequently too. On the contrary, arterial hypertension wasn't controlled better than the general population of...
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...
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...
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...
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...
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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2 Rokyta, R.
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