Projects / Programmes
Pharmacological protection against ischemic-reperfusion injuries and against degenerative processes in brain and cardiovascular tissues
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B740 |
Biomedical sciences |
Pharmacological sciences, pharmacognosy, pharmacy, toxicology |
Cardioprotectants, neuroprotectants, ischemia, reperfusion, hypoxia, ischemic markers, neurotrophins
Researchers (11)
Organisations (1)
Abstract
Pharmacological protection against ischemic-reperfusion injuries and against degenerative processes in brain and cardiovascular tissues
Significance for science
Research project binded two fields of research of injuries that appear during the aging, slow degenerative processes and related hypoxic and ischemic conditions that might be at least common on some basic pathways in cardiovascular as well in central nervous tissues. Our work focused in searching for common principles in those tissues for ischemic processes in both organ systems. Drugs that have potential in decreasing of ischemic injuries are being evaluated in both tissues.
The results of the project explained some of the processes and mechanism of activity of endogenous as well as exogenous pathways of neurotransmitters and cytokines in patophysiological conditions that are simulating the degenerative processes in diseases. Our results propose the use of some recent drugs for indication in decreasing of such processes.
Part of the project dealed with brain cells (astrocytes, preliminary neurons). Astrocytes in constant interactions with neuronal cells play a role during development and in normal brain function as well as in neurodegenerative processes in brain. Our study was focused on the regulation of neurotrophic activity of astrocytes, i.e. an important neuroprotective feature of these cells. Astrocytes represent an important local source of the substances which control the survival of developing neurons, neuronal plasticity in adult nervous system and survival of injured or degenerative neuronal cells. The synthesis of neurotrophins is regulated by a number of factors including neurotransmitters with poorly understood stimulatory activity therefore we study the receptor and intracellular mechanisms involved in the up-regulation of neurotrophins in cultured astrocytes in normal and ischemic conditions. Better knowledge of these processes is the basis for our investigation and understanding the role of astrocytes and their neurotrophic/neuroprotective activity following ischemic insult. Ben Barres, Stanford, explains that saving astrocytes from dying after ischemic injury would be a far more effective strategy than trying to save neurons; glia already know how to save neurons, whereas neuroscientists still have no clue (Barres B, Neuron 60, 430-440, 2008). The present study represents the beginning of long-lasting studies which would enable to get a better insight into pathological processes, triggered by hypoxic/ischemic state and, moreover, searching for pharmacologically active substances with the ability to prevent apoptosis. Part of our study therefore deals with examining neuroprotective mechanisms of the substances with promising cardioprotektive nature.
Hypoxic-reoxygenation as well as ischemic-reperfusion injuries are still one of the research focuses since they influence numerous endogenous patophysiological processes. In our research in isolated heart and arteries we were focused on correlation to unknown endothelium derived hyperpolarizing factor (EDHF), that can be studied in isolated arteries and heart, most probably important also in the central nervous system tissues!
We studied effects of bilitranslocase in processes of cardiovascular protection, a study that was started by prof. Sabina Passamonti from Triest University. Bilirubin is endogenous antioxidant and at the same time a substrate for bilitranslocase, that is specific membrane transporter of bilirubin. Since it is responsible also for transport of flavonoids in brain, we evaluated its role in transport of cardioprotective substances into the heart tissues. Experiments in isolated hearts and coronaries confirm cardioprotective effects of antocians-reach extract in ischemic–reperfusion injuries.
Significance for the country
Project is important for Slovenian biomedical environment for increasing the knowledge and updates in the field of ischemic diseases in central nervous and cardiovascular system. Development of pharmacology and medicine in Slovenia enables equal communication to the world trends and enables researchers to establish more contacts to foreign institution. On the other hand new knowledge also helps to find more application-oriented project to pharmaceutical industry for evaluation of new drugs.
The special focus on evaluation of new drugs and therapies will be important due to strong pressure of pharmaceutical industry for drug prescription for diseases that supposed to be treated chronically. Critical evaluation of such therapies can be done in independent university institution rather in clinical hospitals, too. Such therapies are important especially in aging population in degenerative processes and thus independent researchers that are running research in these fields can influence more critical prescription.
For the local environment the presence of university research represents the major environment for education of new researchers. In the present project 3 young scientists were being educated in pharmacology and also some of graduate student were involved in some parts of research.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
