Protein kinase C activity, metabolic, and hemodynamic changes in cerebral ischemia in the adult rat

Cerebral high energy metabolites and metabolic end products were measured during and following total cerebral ischemia in the rat (TCI). During ischemia, lactate accumulation was greatest in the hippocampus, followed by the cerebral cortex and striatum. Following reperfusion, the rate of lactate clearance was slower in the hippocampus than in the other two regions.; Regional cerebral blood flow (CBF), cerebral plasma volume (CPV) and calculated mean transit time (MTT) were determined following reflow of ischemic tissue. During hyperemia, CPV increased concomitantly with CBF while the MTT remained near control, suggesting that the linear flow rate through the vasculature was unchanged. During hypoperfusion, CPV returned to control values; but, there was a significant increase in MTT.; The finding of normal tissue energy charge, pH{dollar}sb{lcub}rm i{rcub}{dollar}, and concentration of other metabolites during hypoperfusion suggest that hypoperfusion does not result in CBF-metabolic mismatch and implies cerebral hypometabolism during this period.; Protein kinase C (PKC) activity during total cerebral ischemia was investigated in the rat. Translocation of PKC activity from the soluble to the particulate fraction was used as an index of PKC activation. There was a drop in percent particulate PKC activity after 30 minutes of ischemia. There was a 40% decline of the total cellular PKC activity after 20 minutes of TCI. This was not accompanied by an increase in activator-independent activity, indicating PKC was not being converted to protein kinase M. These data suggest that ischemia causes a reduction in cellular PKC activity.; Translocation of PKC activity to the particulate fraction was not observed in the cerebral cortex or hippocampus of reperfused brain for up to 6 hours of recovery following 11-13 minutes of TCI. There was a reduced level of total, soluble and particulate PKC activity in the cerebral cortex corresponding to the decrease observed by 15 minutes of ischemia without reflow. A similar decline in activity was also observed in the hippocampus. No increase in activator-independent activity was observed. These data suggest that PKC was inhibited during cerebral ischemia and this reduced level of PKC activity was maintained throughout 6 hours of recovery. Pathologic activation of PKC was not associated with ischemic damage.