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In Vivo Development of Brain Phosphocreatine in Normal and Creatine‐Treated Rabbit Pups
Author(s) -
Holtzman D.,
Khait I.,
Mulkern R.,
Allred E.,
Rand T.,
Jensen F.,
Kraft R.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732477.x
Subject(s) - phosphocreatine , endocrinology , creatine , medicine , in vivo , white matter , hypoxia (environmental) , nucleoside triphosphate , biology , chemistry , energy metabolism , magnetic resonance imaging , oxygen , biochemistry , nucleotide , microbiology and biotechnology , organic chemistry , radiology , gene
: 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% O 2 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 31 P 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.