Effects of accumulation of phosphocreatine on utilization and restoration of high-energy phosphates during anoxia and recovery in thin hippocampal slices from the guinea pig.

Effects of accumulation of phosphocreatine (P-creatine) on utilization and restoration of high-energy phosphates during anoxia and recovery were studied using thin hippocampal slices from the guinea pig. Incubation of slices with creatine (5 to 30 mM) increased the content of tissue P-creatine, in a linear fashion, and these increases depended on the concentration of creatine and the incubation period to as long as 3 h. Concentration of ATP in the slices was not altered. A high concentration of tissue P-creatine (40 to 100 mmol/kg protein) accumulated by incubation with creatine reduced the rate of ATP exhaustion during anoxia whereas P-creatine itself was rapidly decreased. During reoxygenation after anoxia, concentrations of ATP and P-creatine rapidly recovered in slices preincubated with creatine. Concentrations of P-creatine previously exhausted during anoxia increased to 100 mmol/kg protein after 25 min of reoxygenation whereas the concentration was 35 mmol/kg in the control slice. Elevation of the concentration of P-creatine may therefore prolong the survival time of brain tissue during anoxia and facilitate recovery during reoxygenation.