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 31P-nuclear magnetic resonance (NMR) spectra were acquired in vivo every minute before, during, and after 7 min of breathing 4% O2. 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.
Tsuji
M
M
Joint Program in Neonatology, Harvard Medical School, Boston, MA 02115, USA.
Allred
E
E
Jensen
F
F
Holtzman
D
D
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D003402:Creatine Kinase / Q000378:metabolism; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase