Increased kynurenic acid in the brain after neonatal asphyxia

In the brain, L-kynurenine is an intermediate for the formation of kynureni c acid, a metabolite with neuroprotective activities, and a substrate for t he synthesis of 3-hydroxy-kynurenine, a metabolite with neurotoxic properti es. In the present study, alterations of L-kynurenine, 3-hydroxy-kynurenine and kynurenic acid levels were examined in the brain of neonatal (10 minut es old) rats after 5, 10, 15 or 20 minutes of asphyxia, and in the brain of the corresponding caesarean-delivered controls, using sensitive high-perfo rmance liquid chromatographic methods. Among kynurenines we found a marked time-dependent increase of kynurenic acid levels, a moderately delayed incr ease of 3-hydroxy-kynurenine, and a trend for a decrease of L-kynurenine co ntent. Thus, the brain reacted rapidly to the oxygen deficit by increasing kynurenic acid levels by 44 % already after 5 minutes of asphyxia, and the most prominent elevation of kynurenic acid (302 % of control) was found aft er 20 minutes of asphyxia - the critical time limit of survival. (C) 2001 E lsevier Science Inc. All rights reserved.