P-31-NMR STUDY OF TRANSIENT ISCHEMIA IN RAT HIPPOCAMPAL SLICES IN-VITRO

Intracellular high energy phosphates (HEP) were monitored in rat hippocampal slices in vitro by P-31-NMR during continuous superfusion, no flow and reperfusion in order to model the changes which occur during cerebral ischemia and reperfusion in vivo. With continuous superfusion, stable intracellular HEP resonance signals were observed for over 4 h. When superfusion was stopped, there were rapid decreases in pH and phosphocreatine levels followed by slower loss of ATP. These changes are similar to those observed during cerebral ischemia in vivo by P-31-NMR. Upon reperfusion, the pH returned to normal, but the extent of HEP recovery depended on the length of time superfusion was halted. Following a 10 min ischemic period HEP levels returned to greater than 90% of preischemic values, while following a 16 min ischemic period there was only 60% recovery. Superfusion with low calcium, high magnesium medium significantly improved the recovery of HEP following 16 min of ischemia to 80% of preischemic levels. These data support the hypothesis that calcium influx during and following ischemia can disrupt energy metabolism in the hippocampus, and that magnesium can have a protective action on cellular energy status, perhaps by further blocking calcium influx.