Neonatal asphyxia in rats: acute effects on cerebral kynurenine metabolism.
Two tryptophan metabolites, the anti-excitotoxic N-methyl-D-aspartate (NMDA) receptor antagonist kynurenic acid (KYNA) and the free radical generator 3-hydroxykynurenine (3-HK), have been proposed to influence neuronal viability in the mammalian brain. In rats, the brain content of both KYNA and 3-HK decreases immediately after birth, possibly to ensure normal postnatal functioning of NMDA receptors. Because complications of birth asphyxia have been suggested to be associated with anomalous NMDA receptor function, we examined the acute effects of an asphyctic insult on the brain levels of KYNA and 3-HK in neonatal rats. Asphyxia was induced in animals delivered by cesarean section on the last day of gestation, using the procedure introduced by Bjelke et al. (Brain Res 543: 1-9, 1991). KYNA and 3-HK levels were determined in the brain at seven time points between 10 min and 24 h after asphyxia. Up to 6 h, asphyxia caused 160-267% increases in KYNA levels. In the same tissues, 3-HK levels decreased (significantly at five of the seven time points), demonstrating an asphyxia-induced shift in kynurenine pathway metabolism toward the neuroprotectant KYNA. This shift might constitute the brain's attempt to counter the ill effects of birth asphyxia. Furthermore, the transient increase in the brain KYNA/3-HK ratio in these animals might be causally related to the well-documented detrimental long-term effects of asphyxia.
Ceresoli-Borroni
G
G
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, U.S.A.
Schwarcz
R
R
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
C005045:3-hydroxykynurenine; D007737:Kynurenine