Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils
Excessive stimulation of N-methyl-D-aspartate (NMDA) receptors during ischemia contributes to apoptotic and excitotoxic nerve cell death. Kynurenic acid is a selective antagonist at the glycine co-agonist site of the NMDA receptor complex at low concentration, and it is a broad-spectrum excitatory a...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2007
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| Sorozat: | EUROPEAN JOURNAL OF PHARMACOLOGY
564 No. 1-3 |
| doi: | 10.1016/j.ejphar.2007.02.029 |
| mtmt: | 1078436 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9996 |
| LEADER | 02800nab a2200289 i 4500 | ||
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| 008 | 161123s2007 hu o 0|| zxx d | ||
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| 024 | 7 | |a 10.1016/j.ejphar.2007.02.029 |2 doi | |
| 024 | 7 | |a 1078436 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Gigler Gábor | |
| 245 | 1 | 0 | |a Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils |h [elektronikus dokumentum] / |c Gigler Gábor |
| 260 | |c 2007 | ||
| 300 | |a 116-122 | ||
| 490 | 0 | |a EUROPEAN JOURNAL OF PHARMACOLOGY |v 564 No. 1-3 | |
| 520 | 3 | |a Excessive stimulation of N-methyl-D-aspartate (NMDA) receptors during ischemia contributes to apoptotic and excitotoxic nerve cell death. Kynurenic acid is a selective antagonist at the glycine co-agonist site of the NMDA receptor complex at low concentration, and it is a broad-spectrum excitatory amino acid receptor blocker at high concentration. Kynurenic acid provides neuroprotection in animal models of cerebral ischemia only at very high doses as it hardly crosses the blood-brain barrier. The neuroprotective effect of L-kynurenine sulfate, a precursor of kynurenic acid, was therefore studied because L-kynurenine readily crosses the blood-brain barrier. L-kynurenine sulfate was administered 15 min before permanent focal cerebral ischemia produced by electrocoagulation of the distal middle cerebral artery in mice. L-kynurenine sulfate induced a small decrease in the surface area of the brain infarction (10%, P<0.05) at 30 mg/kg i.p., and it caused strong reductions in infarct size (24-25%, P<0.01) at 100 and 300 mg/kg i.p. Treatment of gerbils with L-kynurenine sulfate at 300 mg/kg i.p. 2 h before a 3-min bilateral carotid occlusion decreased (40%, P<0.01) the pyramidal cell loss in the CAl area of the hippocampus. Furthermore, L-kynurenine sulfate inhibited the ischemia-induced hypermotility (77%, P<0.001), and decreased (50%, P<0.01) the ischemia-induced deterioration of spontaneous alternation, a measure of spatial memory, without altering the rectal temperature. In conclusion, the administration of L-kynurenine can elevate the brain concentration of kynurenic acid to neuroprotective levels, suggesting the potential clinical usefulness of L-kynurenine for the prevention of neuronal loss. (c) 2007 Elsevier B.V. All rights reserved. | |
| 700 | 0 | 1 | |a Szénási Gábor |e aut |
| 700 | 0 | 1 | |a Simó Annamária |e aut |
| 700 | 0 | 1 | |a Lévay György István |e aut |
| 700 | 0 | 1 | |a Hársing László Gábor |e aut |
| 700 | 0 | 1 | |a Sas Katalin |e aut |
| 700 | 0 | 1 | |a Vécsei László |e aut |
| 700 | 0 | 1 | |a Toldi József |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/9996/1/Gigler_G._L_Kyn._u.pdf |z Dokumentum-elérés |