Kynurenic Acid-Enhancing And Anti-Ischemic Effects of the Potent Kynurenine 3-Hydroxylase Inhibitor Fce 28833 in Rodents

Cloning and functional expression of human kynurenine 3‐monooxygenase

“…Notably, KMO appears to be upregulated in inflammatory conditions [3, 15]. It has been proposed that inhibitors of KMO may provide new neuroprotective agents and KMO inhibitors have been found to protect against chemically and electrically induced seizures in rodents and to reduce infarct size in a global ischemia model in gerbils [16, 17].…”

4-Chloro-3-Hydroxyanthranilate Reduces Local Quinolinic Acid Synthesis, Improves Functional Recovery, and Preserves White Matter after Spinal Cord Injury

“…It should be noted, however, that the beneficial effects of KYNA on QUIN neurotoxicity occur when the ratio of KYNA concentration to QUIN concentration exceeds 3:1 (Foster et al, 1984b;Wirsching et al, 1989;Lekieffre et al, 1990). The results show that endogenous KYNA levels in the guinea pig spinal cord are substantially lower than QUIN concentrations, as has been documented on other brain regions in gerbil, rat, mouse, and human (Moroni et al, 1988;Saito et al, 1993;Speciale et al, 1996). The present results demonstrate that KYNA levels were not enhanced by 4Cl-3HAA treatment.…”

“…In uninjured control guinea pigs, spinal cord KYNA levels were below the minimum sensitivity of the HPLC assay (1 pmol/g) and thereby below the values usually measurable in gerbils (4.1 pmol/g [Speciale et al, 1996]; 50.1-71.6 pmol/g [Saito et al, 1993]) and rats (17.8 Ϯ 2 pmol/g [Moroni et al, 1988]), and well below QUIN concentrations in the sample spinal cord extracts (132 Ϯ 32 pmol/g). At 12 days post-injury, KYNA levels in the guinea pigs that received buffer injections were elevated to 10.6 Ϯ 8.4 pmol/g, while QUIN concentrations had increased to 4674 Ϯ 2321 pmol/g in the same extracts.…”

Inhibition of increased indoleamine 2,3-dioxygenase activity exacerbates neuronal cell death in various CNS disorders

“…KYNA attenuates the ischemic neuronal loss both in vitro and in vivo. Peripherally administered KYNA protects hippocampal CA1 pyramidal neurons in a transient forebrain ischemia model in gerbils [8,9]. Similarly, the increase in endogenous production of KYNA, due to the blockade of conversion of L-KYN to other metabolites, reduces the infarct volumes of the hippocampal CA1 region following ischemia [4,6].…”