Neuroprotective effect of the novel kynurenate analogue SZR-72 in the four-vessel occlusion model in rats

Abstract

Event Abstract Back to Event Neuroprotective effect of the novel kynurenate analogue SZR-72 in the four-vessel occlusion model in rats Levente Gellért1*, Anikó Göblös1, Kitti Sárközi1, Zsolt Kiss1 and József Toldi1 1 University of Szeged, Department of Physiology, Anatomy and Neuroscience, Hungary Measuring the pyramidal cell loss of CA1 hippocampal subfield is a valid tool for assessing the effect of a putative neuroprotectant. The permanent vertebral artery occlusion and temporary carotid ligation (four-vessel occlusion) is a widely accepted intervention to model global cerebral ischaemia. Under ischaemic conditions the lack of glucose and oxygen can, in addition to other outcomes, result in the malfunction of ATP-dependent transporters in neurones and glia. Due to the increased membrane potential of presynaptic neurons the efflux of excitatory amino acids occurs, contributing to the excessive activation of post-synaptic glutamate receptors. Excess synaptic glutamate level contributes to the over-activation of ionotropic NMDA (N-methyl-D-aspartic acid) receptors which mediate an excessive entry of Ca2+, initiating a series of cytoplasmic and nuclear processes that promote glutamate-induced excitotoxicity. The role of endogenous kynurenines and its synthetic derivatives in neurodegenerative disorders is well known. As a glycine-site NMDA antagonist kynurenic acid, L-kynurenine sulphate and glucosamine-kynurenic acid has proved to be neuroprotectant in cerebral ischaemia. In this study we have investigated the potential neuroprotective effect of administration of the novel kynurenate analogue. 1 mmol/kg SZR-72 was administered ip. 1 hour before, and then repeated at two, three, twenty-three, and twenty-nine hours after the carotid ligation. Statistical analysis (ANOVA) revealed a significantly decreased number of Fluoro-Jade B labelled injured CA1 pyramidal neurons counted in one eye-field under 20X magnification on serial sections in the treated group. Spatial dimension of labelled neurones along CA1 region also decreased significantly. Our findings suggest that systemically administered novel kynurenate analogue SZR-72 can readily cross the blood-brain barrier and protects neurones against ischaemic injury. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cellular neuroscience Citation: Gellért L, Göblös A, Sárközi K, Kiss Z and Toldi J (2010). Neuroprotective effect of the novel kynurenate analogue SZR-72 in the four-vessel occlusion model in rats. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00044 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Apr 2010; Published Online: 20 Apr 2010. * Correspondence: Levente Gellért, University of Szeged, Department of Physiology, Anatomy and Neuroscience, Szeged, Hungary, huxley@citromail.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Levente Gellért Anikó Göblös Kitti Sárközi Zsolt Kiss József Toldi Google Levente Gellért Anikó Göblös Kitti Sárközi Zsolt Kiss József Toldi Google Scholar Levente Gellért Anikó Göblös Kitti Sárközi Zsolt Kiss József Toldi PubMed Levente Gellért Anikó Göblös Kitti Sárközi Zsolt Kiss József Toldi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.