title: Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia.
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.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Gellért
authors.forename: János
authors.initials: J
authors.lastname: Fuzik
authors.forename: Anikó
authors.initials: A
authors.lastname: Göblös
authors.forename: Kitti
authors.initials: K
authors.lastname: Sárközi
authors.forename: Máté
authors.initials: M
authors.lastname: Marosi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kis
authors.forename: Tamás
authors.initials: T
authors.lastname: Farkas
authors.forename: István
authors.initials: I
authors.lastname: Szatmári
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.forename: József
authors.initials: J
authors.lastname: Toldi
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000601:surgery*; D002452:Cell Count; D004195:Disease Models, Animal; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D007736:Kynurenic Acid