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Contenu archivé le 2022-12-23

Neuronal cell death (apoptosis) in cerebral ischemia: establishment of novel markers and development of methods for prevention of stroke-caused cell damage

Objectif



The final goals of the project are 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 NMDA receptor antagonist Flupirtine).

The specific aims of this project are: to study the expression of reliable markers for apoptosis in brain areas which are particularly sensitive to ischemia and in an area poorly sensitive to ischemia: cell biological markers (morphology) and molecular biological markers (expression of c-fos, c-jun, ubiquitin, hsp70); to investigate the hypoxic neuronal injury at the molecular level (studies in cultured neurons and studies in animal model); therapy-related studies of the neuroprotective effect of Ca2+channel blockers, NMDA receptor antagonists, radical scavengers.

Preliminary results have revealed that selective NMDA receptor antagonists display a strong neuroprotective effect against ischemic cell damage. One compound turned out to be highly promising: Flupirtine, a centrally-acting non-opioid analgesic which was found to act as a NMDA receptor antagonist. In addition, hypoxic brain injury was found to be associated with changes in the ratio of quinolinic acid to kynurenic acid.

Additional tasks of the project are: investigation of the neuroprotective effect of the newly discovered NMDA receptor antagonist Flupirtine; establishment of whether quinolinic acid is a suitable biochemical parameter which can be used as a measure for a therapy success during treatment of ischemia; establishment of a RIA for quantification of quinolinic acid.

Appel à propositions

Data not available

Régime de financement

Data not available

Coordinateur

Johannes Gutenberg Universität Mainz
Contribution de l’UE
Aucune donnée
Adresse
Duesbergweg 6
55099 Mainz
Allemagne

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Coût total
Aucune donnée

Participants (4)