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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David
This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes, since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important role in neuronal calcium...
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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš ; Horák, Petr (advisor) ; Bilej, Martin (referee) ; Schabussova, Irma (referee)
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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Modulation of synaptic transmission in the development of painful states
Slepička, Jakub ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
My thesis introduces the topic of nociceptive signalisation and processes involved in the formation and spreading of neuropathic pain. This study focuses on the mechanisms of nociceptive synaptic transmission mechanisms in the level of spinal dorsal horn and its modulation by paclitaxel, a chemotherapeutic drug inducing neuropathic changes. The attention is put especially on the possibility of glial activity participation in paclitaxel side effects. This idea stems from the existing hypothesis of the functional connection between TLR4 and TRPV1 receptor activity. TRPV1 is well known for its participation in chemical, thermal and nociceptive sensory transmission. Minocycline antibiotic is considered as an inhibitor of microglial activation therefore it was used for blocking neuroinflammation. The experimental part is comparing an impact of substances applied to the model of tachyphylaxis used for monitoring of nociceptive transmission changes according to decreasing activity of TRPV1 receptors. Electrophysiological recording of miniature excitatory postsynaptic currents from neurons in the Rexed laminae I. and II. of spinal dorsal horn was used. The results of my measurements show that minocycline is able to suppress acute effects of paclitaxel application in vitro if the spinal slice is incubated...
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Spinal trauma in terms of pre-hospital care
VAŠÍČKOVÁ, Denisa
The bachelor thesis deals with spinal trauma in the conditions of pre-hospital emergency care. The objektive of this work is to map out the procedure of paramedics in addressing spinal trauma in the conditions of pre-hospital emergency care. Part of the bachelor thesis is a theoretical and practical part.The theoretical part introduces the reader with the anatomy of the spine, by construction, the functions and the imposition of the spinal cord. Briefly mentioned here is the etiology of injury and the pathophysiology of traumatic injury to the spine and spinal cord. The charter will also focus on the diagnosis of spinal trauma, where anintegral part is anexact anamnesis, clinical examination and imaging methods. This section also describes the procedure of the treatment provided by the medical service and possible cooperation with members of the fire brigade in the patient with spinal trauma. The research part has two main objectives: To findout, chat is the procedure of paramedic in addressing spinal trauma in the conditions of pre-hospital emergency care. Find out what are the most frequently used utilities in the event of injuries leading to spinalinjuries. These targets are detected by the method of qualitative research. Data collection was carried out by the technice of means of semi-structured interview. The research sample consists of 10 paramedics of Medicalrescue service of the Highlands region. The investigation has found that paramedics of Medicalrescue service of the Highlands region have gaps in some aspects of spinal cord injury. Overall, the results were satisfactory.
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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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