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Modulation of nociceptive synaptic transmission
Nerandžič, Vladimír ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee) ; Hejnová, Lucie (referee)
Modulation of synaptic transmission in the spinal cord dorsal horn plays an important role in development and maintenance of pathological pain states. The indisputable part of this modulation is conducted via activity of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and the cannabinoid receptor 1 (CB1), expressed on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Under physiological conditions, activation of TRPV1 receptors is pronociceptive while CB1 receptor activation leads to attenuation of nociceptive signalling. However, both receptors share also one endogenous agonist anandamide (AEA) that may be produced from N-arachidonoyl phosphatidylethanolamine (20:4-NAPE). Main objective of this thesis focuses on the effect of 20:4-NAPE on nociceptive synaptic transmission in spinal cord slices under naïve and inflammatory conditions and consequent on the possible interaction of TRPV1 and CB1 receptors. First, 20:4-NAPE application induced significant release of anandamide from spinal cord slices under in vitro conditions. Next, patch- clamp recordings of excitatory postsynaptic currents (mEPSC and sEPSC) from superficial dorsal horn (DH) neurons in acute spinal cord slices were used. 20:4-NAPE application under the physiological...
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The role of nociceptive synaptic transmission modulation
Tyshkevich, Alexandra ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
Chronic pain phenomenon is an important problem in modern medicine. Occurring of this phenomenon is tightly connected with nociceptive transmission and modulation of nociceptive signal on the spinal cord level. Under the pathological conditions such as injury or inflammation this modulation is affected by different types of endogenous molecules with pain enhancing attributes. Important group of these molecules are chemokines, immune system substances, also responsible for immune cells recruitments. However, in pathological states chemokines show ability to modulate nociceptive signal and induce chronic pain. CCL2, in particular, has a significant role in modulation of these processes in the spinal cord. Investigation of the mechanisms by which CCL2 influences the spinal cord and dorsal root ganglion may be an important part for preventing the development of chronic pain. Key words: nociception, pain, spinal cord, chemokines, CCL2
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Behavioral testing of animals after experimental spinal cord injury.
Freislebenová, Hana ; Machová Urdzíková, Lucia (advisor) ; Kriška, Ján (referee)
Spinal cord injury is one of the most serious injury that leads to a decrease in the quality of life both physically and mentally. Although there is currently no effective treatment, great efforts are being made to develop new treatments. The effectiveness of experimental treatment is verified by behavioral tests performed on animal models, where rats are the most suitable ones for this type of injury. Behavioral tests are divided into several groups depending on what the testing is focused on. Locomotor tests examine the function of a locomotive apparatus, motor tests are used to determine the function of skeletal muscles not primarily involved in locomotion, sensory and motor tests test the functionality of sensory and motor apparatus and their interconnection, sensory tests are designed to test responses to sensory stimuli. Electrophysiological tests and functional magnetic resonance imaging are part of a series of special tests that use artificially induced electrical stimuli to measure muscle activity. This thesis is focused on detailed description of selected behavioral tests, their functionality and comparison of their advantages and disadvantages.
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The role of TLR-4 receptors for modulation of nociceptive signalling.
Slepička, Jakub ; Paleček, Jiří (advisor) ; Zímová, Lucie (referee)
The ability to feel pain is subjective, but a crucial factor allowing us to maintain life with minimal body impairment. However, if the pain crosses the physiological signalling function it becomes a life restrictive symptom that is often difficult to treat. Development of pain and its change into pathological chronic symptom and the role of different molecular and cellular mechanisms in this process are best to be studied during its development, nociception. In this work the basic characteristics of nociceptive signalling, with focus on neuropathy, a state originating from nervous system damage is given. The exact mechanisms of neuropathic pain development are not known, which is one of the reasons why these painful states are difficult to treat. Neuroinflammation was lately shown to play an important part in the neuropathy development. In this context a review of Toll-like receptors is given. These receptors have a fundamental role in the innate immunity and their role in the nervous system was documented recently. In this review a focus is given on TLR-4 subtype that was shown to be involved in a modulation of nociceptive signalling. The basic features of this receptor and information about its involvement in neuropathic pain development are given. Studying the role of TLR-4 in different models...
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Case study of the physiotherapy treatmen of a patient after embolisation procedure of spinal arteriovenosus malformation with a nidus in the Th12-L1 segment with developed severe paraparesis of lower limbs
Zámečník, Marek ; Neuwirthová, Svatava (advisor) ; Vrhel, Otakar (referee)
Autor: Marek Zámečník Title: Case study of the physiotherapy treatment of a patient after embolisation procedure of spinal arteriovenous malformation with a nidus in the Th12-L1 segment with developed severe paraparesis of lower limbs. Objective: The aim of this work is a summary of theoretical and practical knowledge, approach the issue of spinal arteriovenous malformations. And from the perspective of a physiotherapist to manage a case report of a patient who underwent embolisation treatment of spinal arteriovenous malformation of ThL spine, after which developed severe paraparesis of lower limbs. Methods: The work is divided into two parts - general (theoretical) and special (practical). Theoretical part is based on the research of specialised literature and summarises the basic information about spinal cord lesions and in great detail about the arteriovenous malformation of spinal cord, about diagnostics and treatment of individual types of malformations and finally a physiotherapy of this kind of diagnosis. Practical part documents the process of physiotherapy of the patient after embolisation treatment of spinal arteriovenous malformation with developed severe paraparesis of lower limbs. Results: The therapy reached the best results in the area of better overall condition of the patient,...
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The case study of physiotherapeutical treatment of a patient with diagnosis edema and shock of cervical spinal cord
Brichtová, Eva ; Říha, Michal (advisor) ; Hankovcová, Eva (referee)
Title: The case study of physiotherapeutical treatment of a patient with diagnosis edema and shock of cervical spinal cord. Summary: The topic of the bachelor thesis is a case interpretation of the patient with edema and shock of cervical spinal cord which happened after a car accident. The aim of this thesis is a comprehensive treatment of the theoretical and practilal knowledge in a patient with the above mentioned diagnosis. The general theoretic part processes anatomy of a spine and a spinal cord. This anatomy is followed by description of the spine and spinal cord injury. Further I deal a clinical picture, pathophysiology of spinal cord injury and subsequent rehabilitation in the theoretical part. The special part includes a case interpretation of the patient with edema and shock of cervical spinal cord and a therapy of this demage. The chosen physiotherapy effect is evaluated in a conclusion. Key words: spinal cord, spinal cord injury, rehabilitation, case study
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The role of TRPV1 receptors in chemokine CCL2 induced modulation of nociceptive synaptic transmission at spinal cord level
Adámek, Pavel ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee)
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn is a significant mechanism in the development and maintenance of different pathological pain states. Accumulating evidence indicates that the TRPV1 (transient receptor potential vanilloid 1) receptor and chemokine CCL2 (C-C motif ligand 2) may play a critical role in this process. The aim of this diploma thesis was to investigate the CCL2 induced modulation of nociceptive synaptic transmission in the dorsal horn of spinal cord and the role of the TRPV1 receptors. To investigate this aim patch-clamp recordings of spontaneous and miniature excitatory postsynaptic currents (sEPSC, mEPSC) from superficial dorsal horn neurons in acute rat lumbar spinal cord slices were used. After acute application of CCL2 on the slice preparation from naïve animals, a frequency increase of both sEPSC and mEPSC was present. This CCL2 induced increase in both sEPSC and mEPSC frequency was prevented by the TRPV1 receptor antagonist SB366791 application. No changes were observed in the amplitudes of sEPSC or mEPSC after application of the CCL2, SB366791, or co-application of CCL2 and SB366791. This suggests that the observed changes were mediated predominantly by presynaptic mechanisms. The preliminary results indicate that after chronic constriction...
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Modelovanie ochorenia a štúdium regeneračných procesov v Huntingtonovej chorobe a ALS in vivo
Hruška-Plocháň, Marián
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
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Huntington's disease modeling and stem cell therapy in spinal cord disorders and injury
Hruška-Plocháň, Marián ; Motlík, Jan (advisor) ; Bjarkam, Carsten (referee) ; Roth, Jan (referee)
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
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