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 hypoxia-induced seizures, 5- to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O2 for 8 min. In saline-treated 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 31P nuclear 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/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all 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 prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes.
Holtzman
D
D
Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Khait
I
I
Mulkern
R
R
Allred
E
E
Rand
T
T
Jensen
F
F
Kraft
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003401:Creatine / Q000494:pharmacology*; D004569:Electroencephalography; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D002534:Hypoxia, Brain / Q000150:complications*; D007279:Injections, Subcutaneous; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000378:metabolism*; D011817:Rabbits; D012640:Seizures / Q000209:etiology* / Q000378:metabolism; D013036:Spasms, Infantile / Q000378:metabolism
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine