title: Post-ischemic treatment with L-kynurenine sulfate exacerbates neuronal damage after transient middle cerebral artery occlusion.
abstract: Since brain ischemia is one of the leading causes of adult disability and death, neuroprotection of the ischemic brain is of particular importance. Acute neuroprotective strategies usually have the aim of suppressing glutamate excitotoxicity and an excessive N-methyl-d-aspartate (NMDA) receptor function. Clinically tolerated antagonists should antagonize an excessive NMDA receptor function without compromising the normal synaptic function. Kynurenic acid (KYNA) an endogenous metabolite of the tryptophan metabolism, may be an attractive neuroprotectant in this regard. The manipulation of brain KYNA levels was earlier found to effectively enhance the histopathological outcome of experimental ischemic/hypoxic states. The present investigation of the neuroprotective capacity of L-kynurenine sulfate (L-KYNs) administered systemically after reperfusion in a novel distal middle cerebral artery occlusion (dMCAO) model of focal ischemia/reperfusion revealed that in contrast with earlier results, treatment with L-KYNs worsened the histopathological outcome of dMCAO. This contradictory result indicates that post-ischemic treatment with L-KYNs may be harmful.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Gellért
authors.forename: L
authors.initials: L
authors.lastname: Knapp
authors.forename: K
authors.initials: K
authors.lastname: Németh
authors.forename: J
authors.initials: J
authors.lastname: Herédi
authors.forename: D
authors.initials: D
authors.lastname: Varga
authors.forename: G
authors.initials: G
authors.lastname: Oláh
authors.forename: K
authors.initials: K
authors.lastname: Kocsis
authors.forename: A
authors.initials: A
authors.lastname: Menyhárt
authors.forename: Z
authors.initials: Z
authors.lastname: Kis
authors.forename: T
authors.initials: T
authors.lastname: Farkas
authors.forename: L
authors.initials: L
authors.lastname: Vécsei
authors.forename: J
authors.initials: J
authors.lastname: Toldi
mesh_terms: D000818:Animals; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced / Q000473:pathology*; D007737:Kynurenine / Q000008:administration & dosage* / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D007737:Kynurenine
keywords: 3-HK; 3-hydroxykynurenine; CNS; EEG; I/H; KYNA; L-KYNs; L-kynurenine sulfate; MCAO model; N-methyl-d-aspartate; N-methyl-d-aspartate receptors; NDS; NMDA; NMDAR; PB; QUIN; central nervous system; dMCA; dMCAO; distal middle cerebral artery; distal middle cerebral artery occlusion; electroencephalography; focal cerebral ischemia; glycine co-agonist site; ischemic/hypoxic; kynurenic acid; kynurenines; neuroprotection; normal donkey serum; phosphate buffer; quinolinic acid