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Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn
Špicarová, Diana ; Paleček, Jiří (advisor) ; Vlachová, Viktorie (referee) ; Rokyta, Richard (referee)
7 ABSTRACT Pathological pain states linked to several diseases or tissue damage are often associated with increased sensitivity to stimuli. The main underlying mechanisms of this hypersensitivity are peripheral sensitization of nociceptors and central sensitization in the spinal cord. One of the crucial processes of central sensitization is the modulation of synaptic transmission at the dorsal horn of the spinal cord. Studies included in my doctoral thesis investigate the possibilities of regulation of synaptic strength by cytokine TNFα, insulin and TRPV1 receptors agonist N-oleoyldopamine (OLDA). These three compounds are synthesized in the CNS, while TNFα is produced in the spinal cord notably during neuropathy. TNFα and insulin have a potential to modulate synaptic transmission. Endogenous TRPV1 receptors agonist OLDA can activate spinal TRPV1 receptors, which are highly expressed on central endings of nociceptive dorsal root ganglion (DRG) neurons. TRPV1 receptors are known as integrators of nociceptive stimuli particularly from the studies of peripheral receptors on nociceptors, which could be sensitized by inflammatory mediators and activated by temperature increase or decrease pH that is unlike in the spinal cord. In our experiments miniature excitatory postsynaptic currents (mEPSCs) or evoked EPSCs...
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Intraaortic balloon counterpulsation (research)
Polívková, Denisa ; Rokyta, Richard (advisor) ; Goričan, Karel (referee)
Intraaortic balloon counterpulsation (IABP) is nowadays a standard invasive method of mechanical support of failing heart. The main indications of IABP are severe forms of acute heart failure and cardiogenic shock, e.g. associated with myocardial infarction. The aim of our study was to evaluate IABP-usage in Intensive Cardiac Care Unit (ICCU), characteristics and clinical outcome of IABP- treated patients. Between January 3rd, 2005 and July 5th, 2008 we treated 56 patients with IABP. Main indication for intaaortic balloon pumping was myocardial infarction (both STEMI and non-STEMI) complicated by cardiogenic shock. In time of IABP initiation 91 % of patients needed catecholamine support. All patients underwent coronary angiography. 75 % of patients were mechanically ventilated, 30,4 % were monitored by Swan-Ganz pulmonary catheter. Complications were observed in 10 patients. The mean duration of IABP was 46 hours. ICCU mortality was 30,4 %, in-hospital mortality rate was 42,9 %. In our institution, IABP has become a part of the complex treatment in patients with severe forms of cardiogenic shock complicating myocardial infarction. In-hospital mortality in our group is comparable with literature data.
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Vanilloid receptor TRPV1 in mechanisms of acute pain
Nováková, Karolina ; Vlachová, Viktorie (advisor) ; Kozák, Jiří (referee) ; Rokyta, Richard (referee) ; Kršiak, Miloslav (referee)
2. SUMMARY Tbe vanilloid receptor (also callcd 'capsaicin receptor') ISa nonselective catian chaLUlcl that IS predominantly exprcssed by nociceptive primary sensory neurons. This receptor was tenned vaniUoid receptor subtype 1 (TRPV I) because it became the founding member of the vanilloid receptor subfamily ortransient receptor potential (TRP) channels, a large supeďamily af nonselective cation channels that play important roles in many sensory functions. The TRPV I channel cao be activated by pungcnt vanilJoid compounds like capsaicin ar resiniferatoxln, acid (pH < 6.5), noxious heat (> 43řC), phorbol csters, endogcnous arachidonic acid derivatives, ar depolarizing voltages. Upon activation by capsaicin, TRPV 1 can regulate cellular calcium levels via direct penneatioD (PCJPN. - lO), wbich concomitantly downregulates its own activity and activates different G-protein- and phospholipase C-coupled signaling cascades. Understanding tbese underlying mechanisms is one af the key strategies that offer a way to alleviatr;: neuropathic and inflammatory pain. Although tbe molecular identificatian of tbe TRPV l channels bas greatly facilitated understanding tbc mechanisms ofthermal hyperalgesia associated with inflammation and thase by which vanilloids increase and subsequendy modulate nociceptor activity, there is...
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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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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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Implementation of organ support methods to acute cardiology and its influence on patients' survival.
Bělohlávek, Jan ; Aschermann, Michael (advisor) ; Rokyta, Richard (referee) ; Nečas, Emanuel (referee)
Acute cardiology cares for critically ill patients suffering from organ dysfunctions and failures, which have to be supported by both pharmacological and non-pharmacological, device-related organ support. The thesis deals with implementation of organ support methods to acute cardiology and its influence on patients' survival. Author implemented and scientifically analyzed benefits of ECMO (extracorporeal membrane oxygenation) both in generally critically ill, and in patients with severe right ventricular failure with cardiogenic shock. (...) These findings confirm crucial role of hemodynamic status in the prognosis of the critically ill patients. Noninvasive artificial mechanical ventilation and specialized outpatient facility were also implemented for early postdischarge care for patients, who survive critical illness. Continued extending of organ support measures is a key prerequisite for further cardiac centre developement.
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Experimental bridging of spinal cord injury with hydrogels
Hejčl, Aleš ; Syková, Eva (advisor) ; Rokyta, Richard (referee) ; Filip, Stanislav (referee)
Hydrogels are biomaterials used in the treatment of experimental spinal cord injury (SCI). In a model of acute SCI, we implanted hydrogels based on 2-hydroxyethylmethacrylate (HEMA) and hydroxypropylmethacryla-mide (HPMA). One month after implantation the hydrogels bridged the cavity, adhered well to the spinal cord and created permissive environment, infiltrated with blood vessels, axons and Schwann cells. Physical modifications (e.g. surface charge) of hydrogels may improve bridging of acute SCI. We implanted hydrogels based on HEMA with a surface charge in spinal cord hemisection and compared with a hydrogel without charge. Hydrogels with surface charge improved connective tissue adhesion and growth of axons compared to a hydrogel without charge. Biodegradable hydrogels may bridge a lesion followed by complete re-sorption. In a model of acute SCI we implanted hydrogels based on the copolymer of HPMA and etoxyethylmethacrylate (EOMA) degraded from the periphery, which was substituted with new tissue after 1 month, to the center, comprising amorphous residuals of the hydrogel. Delayed hydrogel implantation may improve bridging of spinal cord le-sion. We implanted hydrogels based on HEMA acutely or in a delayed fashion (after 7 days) in spinal cord transection. Delayed implantation re-duced the volume of...
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The effect of analgesics and their combination with neurotropic drugs on pain and brain mediators
Soukupová, Marie ; Kršiak, Miloslav (advisor) ; Farghali, Hassan (referee) ; Rokyta, Richard (referee)
The first aim was to investigate changes in analgesic efficacy of several analgesics in combination with selected drugs affecting nervous system after systemic administration. The second aim was to ascertain changes of levels of pain mediators in vivo in supraspinal brain structures (in periaqueductal gray matter, central amygdala, striatum) in pain and under the drug influence. The analgesic efficacy of combinations of analgesics with neurotropic drugs was investigated in the writhing test in mice. Interactions between analgesics and neurotropic drugs were evaluated by the isobolographic analysis, which enables to distinguish the supra-additive (synergistic) interactions from solely additive and sub-additive ones. A possible negative effect of neurotropic drugs on motor functions was determined in the rota-rod test in mice. Changes of levels of pain mediators in the brain during pain and under the drug influence in rats were measured by microdialysis in vivo coupled with a high performance liquid chromatography. A model of inflammatory pain induced by intraplantar injection of carrageenan and a model of neuropathic pain produced by a spared sciatic nerve injury model were used in rats. We evaluated pain in plantar and von Frey filament test. Our microdialysis experiments revealed that inflammatory pain...
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Cortical electrical stimulation and pain
Rusina, Robert ; Rokyta, Richard (advisor) ; Haninec, Pavel (referee) ; Paleček, Jiří (referee)
The aim of the study was to examine effects of sensorimotor cortex stimulation on pain in animal. A behavioral model investigated pain thresholds in deafferentated rats depending on cortex stimulation and two neurophysiological models studied different components of the jaw opening reflex (JOR) and tooth pulp evoked potentials (TPEPs) following cortical stimulation. The behavioral model used 18 deafferentated (dorsal root rhizotomy) rats and 14 controls. Pain thresholds were measured before and after cortical stimulation using plantar test and tail-flick latencies. In the neurophysiological model, rats were implanted with tooth pulp, cerebral cortex, and digastric muscle electrodes. 15 animals were divided into three groups, receiving 60 Hz, 40 Hz and no cortical stimulation, respectively. TPEPs were recorded before, one, three and fi ve hours after continuous stimulation. 10 other rats were submitted to recordings after a single tooth pulp stimulation, while in 5 more rats we administrated conditioning and test stimulation. TPEPs and digastric EMG were simultaneously recorded. A multiresolution denoising method was used for signal processing. Our results show a similar effect of the stimulation in man and experimental animals despite the differences in the organization of the cerebral cortex. Our results...
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