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

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

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36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)182-187
Number of pages6
JournalEuropean Journal of Pharmacology
Volume667
Issue number1-3
DOIs
Publication statusPublished - Sep 30 2011

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Keywords

  • 4VO model
  • Ischemic brain damage
  • Kynurenine
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmacology

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