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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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Extracellular space diffusion parameters and metabolism in the rat somatosrensory cortex during recovery from trabsient global ischemia and hypoxia
Zoremba, Norbert ; Syková, Eva (advisor) ; Mareš, Pavel (referee) ; Rokyta, Richard (referee)
Content Abstract .................................................................. ..... ...... ............................ .... 2 Introduction ............................................ ........................................ .................. 4 Aims .................. ................. ................................ ....... ..... . ............ .......... 6 Methods ............................................... ......................................................... ... 7 Results ................ ............................................................................ .................. 9 Discussion .. ... ............... .. ......... .. .......................... ............................. ... ............. 13 References ....... ................................................................ ....................... ........ 20 List of Publications ............. .... .. ............... .. ... .. .......... .. ... ............................... .... 22 Abstract The extracellular space (ECS) of the brain represents the microenvironment of nerve cells and enables the diffusion of neuroactive substances among neurons, axons and glia. Changes in the ECS diffusion parameters during ischemia are well known, but information about changes in ECS diffusion and energy-related metabolite...
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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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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 changes of hearing function during the postnatal development
Groh, Daniel ; Syka, Josef (advisor) ; Rokyta, Richard (referee) ; Dlouhá, Olga (referee) ; Valvoda, Jaroslav (referee)
8 přítomny spontánní otoakustické emise (SOAE). Amplitudy otoakustických emisí TEOAE, jejichž frekvenční spektrum leželo v rozmezí 0,5-8 kHz, se výrazně snižovaly s věkem. Vysokofrekvenční sluchová ztráta se tedy může odrazit ve snížení amplitudy TEOAE měřené na nízkých a středních frekvencích. Vyhodnocení sluchových ztrát v rozšířeném frekvenčním pásmu spolu se záznamem TEOAE a SOAE může napomoci detekci počínajících sluchových poruch v dětském věku, které nemohou být odhaleny klasickou audiometrií s frekvencí do 8 kHz. Ve studii byly dále hodnoceny audiologické charakteristiky dětí a mladistvích trpících tinnitem různé etiologie a porovnány s obdobnými vyšetřeními u kontrolní skupiny stejně starých dobrovolníků. U jednotlivých pacientů nebyla nalezena korelace mezi původem tinnitu a výsledky audiometrických testů, tj. tónovým audiogramem a výsledky záznamu evokovaných otoakustických emisí (TEOAE a DPOAE). Byl zjištěn pouze významně nižší výskyt SOAE (44,6 % uší) u mladých pacientů s tinnitem v porovnání s 62,5% uší v kontrolní skupině dětí a mladistvých. Nicméně byla pozorována silná závislost amplitud a frekvenčních charakteristik TEOAE a DPOAE na stupni sluchové ztráty bez ohledu na zdroj tinnitu. SUMMARY Experimental part Mechanisms of age-related hearing loss were studied in two rat strains. In aged...
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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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Diffusion parameters of brain tissue during ischemia and during status epilepticus
Šlais, Karel ; Syková, Eva (advisor) ; Otáhal, Jakub (referee) ; Rokyta, Richard (referee) ; Dezortová, Monika (referee)
Difusion of neuroactive substances in the extracellular space (ECS) is constrained by two factors: extracellular space volume and geometry. We have shown changes of diffusion parameters and extracellular concentrations of energetic metabolites and glutamate in two pathological states accompanied by significant ECS volume changes - in combined hypoxia/ischemia and in status epilepticus. In the model of hypoxia/ischemia, we have shown time courses of diffusion parameters, concentrations of glucose, lactate, lactate/pyruvate ratio and glutamate during hypoxic/ischemic insult and after reperfusion. The time course of glutamate extracellular concencetration in transient hypoxia/ischemia correlated well with time course of changes in diffusion parameters. The decrease in the ECS volume fraction can therefore contribute to an increased accumulation of toxic metabolites, which may aggravate functional deficits and lead to damage of the central nervous system. In the model of pilocarpine-induced status epilepticus our results show changes in the extracellular space diffusion parameters, K+, energy-related metabolites and glutamate during the initiation and first hours of the propagation. Our results also show that the first minutes after a pilocarpine injection are followed by an increase in extracellular K+ and a...
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název v anglickém jazyce není uveden
Glogarová, Kateřina ; Syková, Eva (advisor) ; Langmeier, Miloš (referee) ; Rokyta, Richard (referee)
Magnetic resonance imaging (MRI) provides a useful noninvasive method to study the long-term migration and fate of transplanted stem cells in the central nervous system in vivo. Grafted adult as well as embryonic stem cells (ESCs) labeled with superparamagnetic nanoparticles survive in the host organism and migrate preferentially into a lesion site, where they populate the damaged nervous tissue. The migration is not affected by the route of administration; the lesion is populated with the same number of cells after intracerebral grafting as after intravenous injection. Less than 3 % of transplanted mesenchymal stem cells (MSCs) in a cortical photochemical lesion differentiated into neurons and none into astrocytes, while most ESCs (70 %) differentiated into astrocytes and only 5 % into neurons. The intravenous injection of MSCs or of the mononuclear fraction of the bone marrow, which includes hematopoietic and nonhematopoietic stem cells, progenitors and lymphocytes (BMCs), as well as the mobilization of endogenous BMCs with G-CSF (granulocyte colony stimulating factor) significantly improved the recovery of hind limb motor function and sensitivity in rats with a spinal cord compression lesion and significantly increased the spared white matter volume in the center of the lesion. The recovery was most...
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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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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...
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