REGIONAL-DEVELOPMENT OF GLUTAMATE-N-METHYL-D-ASPARTATE RECEPTOR-SITESIN ASPHYXIATED NEWBORN-INFANTS

The N-methyl-D-aspartate (NMDA) subclass of glutamate receptors was ex amined in newborn infants dying between 25 weeks' gestation and term, either from acute cerebral hypoxia, or from other noncerebral conditio ns incompatible with Life. Frontal, occipital, temporal, and motor cor tex tissue samples were obtained at autopsy (post mortem delay: median , 45.9 hr; range, 24-96 hr) and frozen for subsequent [H-3]MK801 homog enate binding assays. Whereas no significant variation was observed in Ligand affinity (K-D,), in all cases receptor density (B-MAX) increas ed with gestational age, in occipital cortex (27 weeks, B-MAX = 222 +/ - 44 fmol.mg protein(-1); 39 weeks, 439 +/- 42 fmol mg protein(-1)), b ut not in motor or temporal cortex. The gestational-age increase also occurred in control frontal cortex (27 weeks, 284 +/- 80; 39 weeks, 56 7 +/- 40 fmol.mg protein(-1)), but was significantly less marked in fr ontal cortex in hypoxia cases (27 weeks, 226 +/- :90; 39 weeks, 326 +/ - 47 fmol.mg protein(-1)). in all cortical areas except temporal, the maximal response to glutamate did not vary across case groups. Hypoxia cases showed an increased response to glutamate enhancement selective ly in temporal cortex. Binding site density did not correlate with deg ree of hypoxia as assessed pathologically, suggesting that receptor di fferences preceded the hypoxic episode. Regional differences in glutam ate-NMDA receptor sites may underlie increased vulnerability to hypoxi a at birth.