In vivo development of brain phosphocreatine in normal and creatine-treated rabbit pups

To study the effects; of creatine (Cr) on brain energy metabolism and on hy poxia-induced seizures, 5-to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O-2 for 8 min. In saline-trea ted controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60 % at 20 days in Cr-treated pups. In surface coil-localized brain P-31 nucle ar magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups;, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/N TP ratio was very low in GM at 5 days but reached adult levels by 15 days i n controls. In WM, the ratio increased steadily from 5 to 30 days of age. I n Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at a ll ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prev ents hypoxic seizures. These results suggest that mature levels of PCr and/ or Cr in brain limit EEG activation either directly or indirectly by preven ting hypoxic metabolic changes.