Previous studies have shown that in utero hypoxia results in brain cell membrane dysfunction and alters N-methyl-D-aspartate (NMDA) receptor characteristics in fetal guinea pigs. The present study tests the hypothesis that modification of brain cell membrane function during in utero hypoxia persists following recovery. Six pregnant guinea pigs at term were exposed to 7% oxygen for 1 hour. Brain tissue obtained from fetal guinea pigs immediately after in utero hypoxia was compared to that of fetuses exposed to hypoxia but allowed to recover in utero for 24 hours. ATP and phosphocreatine (PCr) levels were determined biochemically as indices of brain tissue energy metabolism. ATP and PCr levels were significantly higher in the recovery group compared to the hypoxic group(5.22±0.95 vs. 1.5±0.02 and 3.73±0.28 vs. 0.66±0.17 μ mol/g brain, respectively, p<0.01). Brain cell membrane Na+,K+-ATPase activity was measured as an index of brain cell membrane function. The recovery group demonstrated a significantly higher activity of Na+,K+-ATPase compared to the hypoxic group(35.1±4.0 vs. 25.2±7.0 μ moles Pi/mg protein/hr, p<0.05).3[H]MK-801 binding (2.5-50 nM) in the presence of glutamate and glycine was performed as an index of NMDA receptor modification. Receptor number(Bmax) in the recovery group was similar to the hypoxic group(1.28±0.04 vs 1.25±0.18 pmol/mg protein). In addition receptor dissociation constant (Kd) was similar in the two groups (5.61±0.30 vs 4.94±0.84 nM). This preliminary data show that following recovery from in utero hypoxia, brain cell energy metabolism and brain cell membrane function improve, but that hypoxia-induced alterations in NMDA receptor characteristics persist. We speculate that alterations in the NMDA receptor following in utero hypoxia may contribute to delayed brain cell injury despite recovery of cellular energy metabolism and cell membrane function.

(Funded by NIH HD 20337).