Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.

The present study tested the hypothesis that the increase in extracellular striatal dopamine during hypoxia is least partly associated with activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors. Studies were performed in anesthetized and mechanically ventilated 2-3 days old piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressure was measured optically by oxygen dependent quenching of phosphorescence, and extracellular striatal dopamine was measured using in vivo microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3 Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically significant increase in extracellular dopamine, to 1050 +/- 310% of control, was observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in the perfusate significantly decreased the levels of extracellular dopamine during hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095 of control, respectively. The presence of NBQX caused a statistically significant decrease, by about 30%, in the extracellular dopamine compared to control, only at the end of the hypoxic period. It can be concluded that in striatum of newborn piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be modulating the changes in extracellular levels of dopamine. The NMDA receptor antagonist, MK-801, may exert part of its reported neuroprotective effect to hypoxic stress in striatum by decreasing the levels of extracellular dopamine.

Effect of dithiothreitol on lipid peroxidation induced modification of NMDA receptor in fetal guinea pig brain.

The present study examines if the NMDA receptor modification induced by lipid peroxidation is mediated through its redox site and is therefore reversible by dithiothreitol (DTT) by performing [3H]MK-801 binding in the fetal guinea pig brain. P2 membrane fractions were prepared from fetal guinea pig brains and were peroxidized in vitro by 100 microM ascorbate and 25 microM ferric chloride for 20 min. Control and peroxidized membranes were then incubated with 100 microM DTT for 30 min at 37 degrees C. [3H]MK-801 binding was performed in DTT treated and untreated membranes in the presence of 100 microM each of glutamate and glycine. In addition, to study the glutamate- and glycine-dependent activation, [3H]MK-801 binding was determined in the absence (basal) and presence (activated) of glutamate and glycine. Bmax (number of binding sites) and Kd (affinity) of the binding sites were used as indices of NMDA receptor modification and its reversibility by DTT. After lipid peroxidation, the Kd value increased from 4.44 +/- 0.12 in control to 10.39 +/- 1.78 nM (P < 0.01) suggesting decreased affinity following lipid peroxidation. Following treatment with DTT, there was no significant change in Kd, but Bmax was significantly (P < 0.007) decreased in the peroxidized membrane. This suggests that DTT did not improve the affinity of the NMDA receptor of the lipid peroxidized membrane but may have a deleterious effect by reducing the number of binding sites. However, in the control membrane DTT significantly increased the affinity (P < 0.004) and the Bmax (P < 0.01) of the NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

[Metabolic kinetics in the brains in infants with IUGR, respiratory distress syndrome, seizures and asphyxia].

31-P magnetic resonance spectroscopy (MRS) allows noninvasive measurements of cerebral phosphorus compounds: ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME) and phosphodiesters (PDE). In this paper we reported our MRS data from the brains of infants with intrauterine growth retardation, respiratory distress syndrome, neonatal seizures or neonatal asphyxia, and discussed the possibilities to prevent brain damage due to these perinatal troubles.