Neuroprotective Effects of L-Kynurenine on Hypoxia—Ischemia and NMDA Lesions in Neonatal Rats

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Abstract
Kynurenic acid is the only known endogenous excitatory amino acid receptor antagonist in the central nervous system. In the present study, we examined whether increasing brain concentrations of kynurenic acid by loading with its precursor l-kynurenine, or blocking its excretion with probenecid, could exert neuroprotective effects. Neuroprotective effects were examined in a neonatal model of hypoxia–ischemia, and following intrastriatal injection of N-methyl-d-aspartate (NMDA). Seven-day-old rats underwent unilateral ligation of the carotid artery, followed by exposure to 8% oxygen for 1.5 h. l-kynurenine administered 1 h before the hypoxia–ischemia showed a dose-dependent significant neuroprotective effect, with complete protection at a dose of 300 mg kg−1. The induction of c-fos immunoreactivity in cerebral cortex was also blocked by this dose of l-kynurenine. Probenecid alone had moderate neuroprotective effects, while a combination of a low dose of probenecid with doses of 50–200 mg kg−1 of l-kynurenin...