|
|
Excitation-Contraction and Excitation-Transcription Coupling in Vascular Smooth Muscle Cells: Alterations in Experimental Hypertension and Vascular Remodeling
Misárková, Eliška ; Zicha, Josef (advisor) ; Hock, Miroslav (referee)
Vascular smooth muscle cells (VSMCs) express considerable phenotype plasticity. They are able to change their phenotype in vivo if necessary. It is important to know that during this phenotype switch the expression of transport proteins and channels is modified, which results in significant alteration of Ca2+ signaling in smooth muscle cells. In differentiated cells, which represent contractile phenotype, there are dominant rapid, transient events in intracellular Ca2+ concentration (Ca2+ i), while the resting cytosolic Ca2+ i concentration is low. In differentiated cells these Ca2+ i events are mainly caused by two components of the Ca2+ signalling pathways: 1) extracellular Ca2+ influx via L-type voltage-gated Ca2+ channels (L-type VGCC) in plasma membrane, and 2) depletion of intracellular Ca2+ stores via ryanodin receptors located on sarcoplasmic reticulum. Rapid Ca2+ i oscillations are quickly reduced by numerous Ca2+ ATPases of sarco/endoplasmic reticulum and plasma membrane. Proliferating vascular smooth muscle cells are characterized by a long-lasting Ca2+ i oscillations accompanied by sustained elevation of basal intracellular Ca2+ concentration. During phenotype switch from contractile phenotype to proliferative phenotype there is decreased Ca2+ ATPase activity, and store-operated Ca2+...
|
|
|
Mesenchymal stem cells for treatment of spinal cord injury
Dubišová, Jana ; Kubinová, Šárka (advisor) ; Hock, Miroslav (referee)
Poranenie miechy a jeho terapia pomocou mezenchymálnych kmeňových buniek Abstract Patients with serious spinal cord injury (SCI) have a little chance of a full return to their original life. This kind of injuries leaves lifelong consequences as on the patients themselves, as well as their surroundings and family. Considerable financial resources are, worldwide, granted for reintegratation of these patients into society. This work focuses on the description of spinal cord injury, its complexity and the possibility of treatment by new therapeutic methods of mesenchymal cells. The first section discusses the severity of spinal cord injury and its pathophysiology with the performance of subsequent clinical phases. The second part is dedicated to new treatment methods and approaches, with an emphasis on cell therapy. The third part presents treatment method using mesenchymal stem cells (MSCs), which immunomodulatory and anti-inflammatory properties, such as their ability to migration to the injured area and the possibility of genetic modification, made them a great candidates for the treatment of serious injuries. Keywords Spinal cord injury, stem cells, mesenchymal stem cells, cell therapy, regenerative medicine
|
|
|
NMDA receptors in astrocytes: their role in ischemic brain injury
Valný, Martin ; Anděrová, Miroslava (advisor) ; Hock, Miroslav (referee)
Glutamate is the main excitatory neurotransmitter in the mammalian brain, and its transmission is responsible for higher brain functions, such as learning, memory and cognition. Glutamate action is mediated by variety of glutamate receptors, of which N-methyl-D-aspartate (NMDA) receptors are the most remarkable due to their high Ca2+ permeability and complex pharmacology. Despite the widespread expression of NMDA receptors in astroglial cells in different brain regions, they have been studied mostly in neurons. Therefore, the role of astroglial NMDA receptors under physiological conditions as well as in pathological states, such as cerebral ischemia, is not fully understood. The aim of this work was to elucidate the presence, composition and function of these receptors in astrocytes under physiological conditions and after focal cerebral ischemia. For this purpose, we used transgenic (GFAP/EGFP) mice, in which astrocytes express enhanced green fluorescent protein (EGFP) under the control of human promotor for glial fibrillary acidic protein (GFAP) enabling astrocyte isolation and their collection via fluorescence-activated cell sorting. We performed single-cell RT-qPCR analysis of astrocytes isolated from the cortex of adult mice. The analyzed cells were isolated from the uninjured brains of 50...
|
|
|
Cholinergic regulation of ion transport in the large intestine
Hock, Miroslav ; Pácha, Jiří (advisor) ; Moravec, Jan (referee) ; Kolínská, Jiřina (referee)
anglicky Acetylcholine is one of the most important mediators of enteric nervous system involved in the regulation of ion transport in the large intestine. Although, recently, plenty of new evidences of various expression of ion transport proteins in distal and proximal colon was published, there still lacks an electrophysiological study comparing these parts of colon considering all that new findings. The aim of this study was thus to compare cholinergic regulation of ion transport in distal and proximal colon. We measured responses of distal and proximal colon in Ussing chambers by voltage-clamp method. The colonic epithelium was clamped to 0 mV and responses were recorded as changes of short-circuit current (SCC). Instead of acetylcholine we used its stable analogue carbachol. Data were processed and analyzed using a VBA code I wrote for this purpose for MS Excel 2007. We confirmed that carbachol acts directly on epithelial cells via muscarinic acetylcholine receptors in both, distal and proximal colon. These responses to carbachol were not influenced by inhibitors of Cl- channels situated in apical membrane (CFTRinh-172 and niflumic acid). Inhibition of basolateral influx of Cl- by serosal Ba2+ and furosemid reduced responses to carbachol in both, distal and proximal colon. Inhibitors of K+...
|
|
|
Interactions between gut microorganisms and brain
Fajstová, Alena ; Pácha, Jiří (advisor) ; Hock, Miroslav (referee)
Intestinal microbiota communicates with brain via various cooperating pathways including neuronal, endocrine and immune. Pathogenic and commensal bacteria produce great amounts of neurotransmitters and various other metabolites which can interact with brain. Presence of bacteria can also induce immune system response which can influence brain through cytokines and other mediators. Last but not least the communication can be mediated through nerves, especially the vagus nerve. The brain can influence the intestines through sympathic and parasympathic efferent nerves and through hormones. Gut colonization by nonpathogenic commensal bacteria is crucial for proper brain development. If this doesn't happen in certain period psychiatric disorders such as depression or autism can occur later in life. Various pathological conditions might be ameliorated or fully reversed by administration of probiotic bacteria. Aim of this thesis is to briefly review factors influencing gut microbiota, its influence on the brain development and the role of probiotics in the therapy of intestinal and psychiatric diseases. Keywords: gut microbiome, brain, neuroendocrine regulation, probiotic, neurotransmitter
|
|
|
Effect of intestinal microflora on the activity of higher brain centers
Arnold, Tomáš ; Hock, Miroslav (advisor) ; Melkes, Barbora (referee)
Abstract Intestinal microflora consists of large bacterial community that resides in the intestines, especially the colon, and lives in symbiosis with the host. It consists mainly representatives of the four bacterial strains (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria). It has already been shown that the proportional representation of the bacterial strains in time does not change much, but the research of the last decade have shown irrefutable effect between the change of diet and composition of the intestinal microflora. In addition, there is evidence of changes in the representation of bacterial strains in the course of development of certain intestinal pathologies such as inflammatory bowel disease. More and more are starting to emerge papers describing the influence of altered intestinal microflora respectively its representatives, on the activity and function of the CNS. This interaction of the digestive system and CNS seems to be bidirectional and mediated by several different pathways. Finally, it shows that dysbiosis of the intestinal microflora promotes anxiety and depression that can lead to the urge to prematurely terminate life. The aim of this work is to provide a comprehensive view of this relatively young, but also very interesting...
|
|
|
Interactions between gut microorganisms and brain
Fajstová, Alena ; Pácha, Jiří (advisor) ; Hock, Miroslav (referee)
Intestinal microbiota communicates with brain via various cooperating pathways including neuronal, endocrine and immune. Pathogenic and commensal bacteria produce great amounts of neurotransmitters and various other metabolites which can interact with brain. Presence of bacteria can also induce immune system response which can influence brain through cytokines and other mediators. Last but not least the communication can be mediated through nerves, especially the vagus nerve. The brain can influence the intestines through sympathic and parasympathic efferent nerves and through hormones. Gut colonization by nonpathogenic commensal bacteria is crucial for proper brain development. If this doesn't happen in certain period psychiatric disorders such as depression or autism can occur later in life. Various pathological conditions might be ameliorated or fully reversed by administration of probiotic bacteria. Aim of this thesis is to briefly review factors influencing gut microbiota, its influence on the brain development and the role of probiotics in the therapy of intestinal and psychiatric diseases. Keywords: gut microbiome, brain, neuroendocrine regulation, probiotic, neurotransmitter
|
|
|
Effect of intestinal microflora on the activity of higher brain centers
Arnold, Tomáš ; Hock, Miroslav (advisor) ; Melkes, Barbora (referee)
Abstract Intestinal microflora consists of large bacterial community that resides in the intestines, especially the colon, and lives in symbiosis with the host. It consists mainly representatives of the four bacterial strains (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria). It has already been shown that the proportional representation of the bacterial strains in time does not change much, but the research of the last decade have shown irrefutable effect between the change of diet and composition of the intestinal microflora. In addition, there is evidence of changes in the representation of bacterial strains in the course of development of certain intestinal pathologies such as inflammatory bowel disease. More and more are starting to emerge papers describing the influence of altered intestinal microflora respectively its representatives, on the activity and function of the CNS. This interaction of the digestive system and CNS seems to be bidirectional and mediated by several different pathways. Finally, it shows that dysbiosis of the intestinal microflora promotes anxiety and depression that can lead to the urge to prematurely terminate life. The aim of this work is to provide a comprehensive view of this relatively young, but also very interesting...
|
|
|
Changes in neuroglia in degenerative disorders of the central nervous system
Kirdajová, Denisa ; Zach, Petr (advisor) ; Hock, Miroslav (referee)
Neurodegenerative diseases are a serious disorders of the central nervous system characterized by neuronal loss with a subsequent damage of the brain. This damage may have diverse consequences like a gradual loss of memory and intellect, problems with musculoskeletal system and not least death. Causes of these diseases are not yet fully understood. In addition to neurons neuroglia also plays an important role in these diseases of the central nervous system. In neurodegenerative diseases are astrocytes, oligodendrocytes, microglia and NG2 cells involved in their many aspects. They participate in the protective as well as in the detrimental aspect of these diseases. This work, therefore, presents an overview of previously acquired knowledge of neuroglia in various types of degenerative disorders of the CNS (Alzheimer`s disease, Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, Wernicke encephalopathy, HIV associated dementia, frontotemporal dementia, vascular dementia). Powered by TCPDF (www.tcpdf.org)
|
|
|
Mesenchymal stem cells for treatment of spinal cord injury
Dubišová, Jana ; Kubinová, Šárka (advisor) ; Hock, Miroslav (referee)
Poranenie miechy a jeho terapia pomocou mezenchymálnych kmeňových buniek Abstract Patients with serious spinal cord injury (SCI) have a little chance of a full return to their original life. This kind of injuries leaves lifelong consequences as on the patients themselves, as well as their surroundings and family. Considerable financial resources are, worldwide, granted for reintegratation of these patients into society. This work focuses on the description of spinal cord injury, its complexity and the possibility of treatment by new therapeutic methods of mesenchymal cells. The first section discusses the severity of spinal cord injury and its pathophysiology with the performance of subsequent clinical phases. The second part is dedicated to new treatment methods and approaches, with an emphasis on cell therapy. The third part presents treatment method using mesenchymal stem cells (MSCs), which immunomodulatory and anti-inflammatory properties, such as their ability to migration to the injured area and the possibility of genetic modification, made them a great candidates for the treatment of serious injuries. Keywords Spinal cord injury, stem cells, mesenchymal stem cells, cell therapy, regenerative medicine
|
guest ::
