PHOSPHOCREATINE AND ATP REGULATION IN THE HYPOXIC DEVELOPING RAT-BRAIN

Decreased brain ATP and phosphocreatine (PCr) concentrations and intracellular pH were compared in hypoxic 4-, 10-11, and 24-25-day-old rats. Surface coil P-31-nuclear magnetic resonance (NMR) spectra were acquired in vivo every minute before, during, and after 7 min of breathing 4% O-2. At all ages PCr decreased rapidly, At the two younger ages, the nucleoside triphosphate signal was still 80-85% of pre-hypoxic values, indicating 20-30% decrease in ATP, when PCr was almost fully depleted. At 24-25 days, PCr initially decreased 40-50% with an ATP loss of about 30%. Then, PCr and ATP decreased simultaneously. The decrease in brain pH was greatest at 24-25 days. More electrocortical seizure activity during hypoxia was seen at 10-11 days than at other ages. Seizure activity was seen only when ATP was less than 20% depleted and was not associated with more rapid decreases in ATP or PCr. At all ages, loss of electrocortical activity occurred when ATP was about 30% depleted. Brain creatine kinase catalyzed flux, measured by the NMR saturation transfer experiment before the hypoxic period, was 4-fold higher at 24-25 days than at 4- or 10-11 days. In conclusion, the temporally coupled depletion of PCr and ATP during hypoxia, which is characteristic of the mature brain, is seen only after the maturational increase in brain CK activity.