Applied and Basic Physiology and Pathophysiology in Medicine

The research program aims at understanding the mechanisms of aging in the field of neurodegenerative diseases, neurovascular coupling and interactions between the neuronal function and cardiovascular system. Providing a broad spectrum of research methods and techniques and bringing together researchers from basic science and clinical research warrants successful interdisciplinary approach with horizontal and vertical integration of this very complex research field. Basic mechanisms of degeneration will be studied on cellular level such as cell cultures of neurons, astrocytes, neuron/astrocyte co-cultures, endothelial cells and hepatocytes using methods of biochemistry, molecular biology, micro-spectrofluorimetry and confocal microscopy. The main contribution to science will be identification of mechanisms of cellular damage by high glucose level, oxidative stress and drugs used for treatment of mental disorders. We will also study the effects of CO on neurons and astrocytes as well as the effects of hyperbaric oxygenation on cells and in vivo. Hyperbaric oxygenation and breathing pure oxygen will be used in the study of potential use of oxygen as a contrast agent in MR imaging. Several contrast agents based on Gd salts have already been banned, and especially in the elderly a risk of renal failure caused by Gd is relatively high. MR imaging will be used in the study of neurodegenerative disorders and in following the outcome of stem cell therapy of cardiomyopathy. Neurodegeneration and cardiovascular disease are the hallmark of aging process, and they share several causative mechanisms. Hyperglycemia is involved in both processes. Effects of acute hyperglycemia will be studied on cell cultures and in vivo on patients with diabetes type I. Those effects are poorly known, but may have a profound effect on brain function and structure. Hyperglycemia is also involved in micro and macroangiopathies as well as in heart failure. We will continue our research in the treatment of dilatative cardiomyopathy with stem cells and follow up by using cardiac MRI. MRI is a safe and effective method to study nervous and cardiovascular system in health and disease. It has excellent space and time resolution and another MR based method, MR spectroscopy (MRS), provides simultaneous information on chemical composition of investigated tissue. We will use both MRI and MRS methods to study neurodegeneration. Especially in the case of Parkinson’s disease introduction of novel techniques such as STIR and quantitative susceptibility mapping (QMS) greatly enhances the resolution of MR images of substantia nigra. In all neurodegenerative and mental disorders MRS provides a deeper insight in the process of neurodegeneration. In collaboration with research team at Johns Hopkins, USA, we can now measure glutamate, glutamine and GABA in brain regions in addition to metabolites detected by standard MRS.

The research program will provide new knowledge of the mechanisms of cell senescence and aging in the field of neurodegenerative diseases, neurovascular coupling and interactions between the neuronal function and cardiovascular system. Bringing together researchers from the field of molecular biology all the way to clinical research and providing a broad spectrum of research methods and techniques available within the program group warrants a successful interdisciplinary approach. Interdisciplinary approach enabling horizontal and vertical integration of this very complex research field is one of the strongest points of the program. Basic mechanisms of degeneration will be studied on cellular level such as primary cell isolation and cell cultures of neurons, astrocytes, neuron/astrocyte cocultures, endothelial cells and hepatocytes using methods of biochemistry, molecular biology, micro-spectrofluorimetry and confocal microscopy. The main contribution to science will be identification of mechanisms of cellular damage by high glucose level, oxidative stress and two drugs used for treatment of mental disorders. We will also study the effects of CO poisoning on neurons and astrocytes as well as the effects of hyperbaric oxygenation on cells and in vivo. Hyperbaric oxygenation and breathing pure oxygen will be used in the study of potential use of oxygen as a contrast agent in MR imaging. Several contrast agents based on Gd salts have already been banned, and especially in the elderly a risk of renal failure caused by Gd is relatively high. MR imaging will be used in the study of neurodegenerative disorders and in following the success of stem cell therapy of dilatative cardiomyopathy. Neurodegeneration and cardiovascular disease are the hallmark of aging process, and they share several causative mechanisms. Hyperglycemia is involved in both processes. Effects of acute hyperglycemia will be studied on cell cultures and in vivo on patients with diabetes type I. Those effects are poorly known, but may have a profound effect on brain function and structure. Hyperglycemia is also involved in micro and macroangiopathies as well as in heart failure. We will continue our research in the treatment of dilatative cardiomyopathy with stem cells and follow up by using cardiac MRI. MRI is a safe and effective method to study nervous and cardiovascular system in health and disease. It has excellent space and time resolution and another MR based method, MR spectroscopy (MRS), provides simultaneous information on chemical composition of investigated tissue. We will use both MRI and MRS methods for study of neurodegeneration. Especially in the case of Parkinson's disease the introduction of novel techniques such as STIR and quantitative susceptibility mapping (QMS) greatly enhances the resolution of neuromelanin imaging in substantia nigra. In all neurodegenerative and mental disorders MRS provides a deeper insight in the process of neurodegeneration. Standard MRS provides information on a few metabolites and transmitters, but using MEGA-PRESS sequence and appropriate post-processing (provided by a collaborator from Johns Hopkins, USA) we can also measure the neurotransmitter GABA and provide more accurate measurements of glutamate glutamine. We are sure that our contribution to science will be evident from several publications in high ranking journals.

The organisation and results of the program group are important for the development of science for several reasons. The combination of complementary research methods and collaboration of researchers from basic science with clinical researchers warrants translation of basic research results into clinical practice. This approach enables engagement in relevant research that contributes to the understanding of a disease and provides clues for therapeutic approaches. In the past we have already shown practical results by introduction new MRI an MRS methods, introduction of cell therapy in cardiomyopathy, use od left ventricular assist device (LVAD) in collaboration with UT, Houston, TX and study of the effects of laminar flow on microcirculation and autonomic nervous system. Our research has also potential impact on economic development. We have produced prototypes of devices, developed new software and filled several patents. Together with collaborators from NIH, Bethesda, USA, our young researcher has developed an innovative approach for automatic segmentation of brain form MR images. Translation of research into practice is also evident from international (US) patent that is already in use by US company CardioSoft, and Slovenian patent for a device to monitor optical nerve microcirculation during neurosurgery. Our researchers are deeply involved in health care system by implementing new knowledge, techniques and approaches for the benefit of individual patients and the population. Publishing in top journals in the field and involvement in executive committees of international professional organizations is important for the promotion of the country. We are also dedicated to excellence in undergraduate, graduate and postgraduate and in the professional development of our staff. Collaboration in international projects and working together with international companies and researchers provides new opportunities and exchange of knowledge. Our goal is to continue with these activities and contribute to the development of science and society.