Exploitable results Neuronal cell death (apoptosis) in cerebral ischemia The project concerns the establishment of novel markers for neuronal cell death(apoptosis) and the development of novel strategies to reduce ischemic neuronal damage in stroke patients (with special reference to the N-methyl-D-aspartate (NMDA) receptor antagonist Flupirtine). Apoptosis, or programmed cell death, is an important biochemical pathway occurring during development, ageing and in cancer cells as well as in cells fighting infections or after exposure to harmful agents. Inducers of apoptosis are physiological activators (eg neurotransmitters), damage related inducers (eg heat shock), therapy-associated agents (eg chemotherapeutic agents) or toxins (eg beta-amyloid peptide). Focusing on the nervous system, apoptosis is the major pathway during development. The excitatory amino acids glutamate and NMDA induce cortical neurons to apoptosis. Glutamate and NMDA activate the ligand-gated calcium ion channels, more specifically the NMDA receptor complex, in a variety of vertebrate neurons. Neuronal cells undergo apoptosis in response to the PrPSc agent. The hypoxic neuronal injury was investigated at the molecular level and the molecular mechanisms causing selective neuronal damage or resistance of other brain areas against stroke-mediated effects were studied in cultured neurons and in animal. Novel techniques were developed for measuring DNA damage and apoptosis. In addition, the neuroprotective effect of the following agents was investigated: calcium channel blockers, NMDA receptor antagonists, and radical scavengers. The research also concerned the establishment whether quinolinic acid is a suitable biochemical parameter, which can be used as a measure for a therapy success during treatment of ischemia, and the establishment of a radioimmunoassay (RIA) for quantification of quinolinic acid. One main result was the elucidation of the mode of action of the anti-apoptotic effects of non-competitive NMDA receptor antagonists and of neuroprotective agents belonging to the group of pyridine derivatives. The role of the anti-apoptotic gene bcl-2 and of cellular glutathione and their modulation by the neuroprotective compounds were clarified. Searching for OpenAIRE data... There was an error trying to search data from OpenAIRE No results available
