Details

Autor(en) / Beteiligte

• Gellért, Levente
• Fuzik, János
• Göblös, Anikó
• Sárközi, Kitti
• Marosi, Máté
• Kis, Zsolt
• Farkas, Tamás
• Szatmári, István
• Fülöp, Ferenc
• Vécsei, László
• Toldi, József

Titel

Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia

Ist Teil von

• European journal of pharmacology, 2011-09, Vol.667 (1), p.182-187

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Global forebrain ischemia results in damage to the pyramids in the CA1 hippocampal subfield, which is particularly vulnerable to excitotoxic processes. Morphological and functional disintegration of this area leads to a cognitive dysfunction and neuropsychiatric disorders. Treatment with N-methyl- d-aspartate receptor antagonists is a widely accepted method with which to stop the advance of excitotoxic processes and concomitant neuronal death. From a clinical aspect, competitive glycine- and polyamine-site antagonists with relatively low affinity and moderate side-effects are taken into account. Endogenous kynurenic acid acts as an antagonist on the obligatory co-agonist glycine site, and has long been at the focus of neuroprotective trials. In the present study, we estimated the neuroprotective capability of a novel kynurenic acid analog in transient global forebrain ischemia, measuring the rate of hippocampal CA1 pyramidal cell loss and the preservation of long-term potentiation at Schaffer collateral-CA1 synapses. The neuroprotective potential was reflected by a significantly diminished hippocampal CA1 cell loss and preserved long-term potentiation expression. The neuroprotective effect was robust in the event of pretreatment, and also when the drug was administered at the time of reperfusion. This result is beneficial since a putative neuroprotectant proven to be effective as post-treatment is of much greater benefit.