Protein kinase C activity in the rat hippocampus after forebrain ischemia: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate.

The influence of transient forebrain ischemia on the temporal alteration of protein kinase C (PKC) activity in the rat hippocampus was analyzed by quantitative autoradiography using [3H]phorbol 12,13-dibutyrate [( 3H]PDBu). As reported previously, the grain density was highest in the strata oriens and radiatum in the CA1 subfield. After transient forebrain ischemia (20 min), the [3H]PDBu binding in the CA1 subfield gradually increased during early recirculation, and became maximum 6-12 h after ischemia, when no microscopic damage of the CA1 pyramidal cells was obvious. Thereafter, grain density decreased and binding activity in the CA1 was lost by approximately 40% 7 days after ischemia, when CA1 pyramidal cells had become necrotic. This indicated a close association of phorbol ester binding sites with CA1 pyramidal cells. By contrast, [3H]PDBu binding sites were unchanged in the stratum radiatum in the CA3 throughout the recirculation, although the number of binding sites in the stratum oriens of the CA3 was decreased during early recirculation period. Seven days after recirculation, in the molecular layer of the dentate gyrus, where granule cells remained intact, [3H]PDBu binding activity increased by 33%, with a higher grain density in the inner region (supragranular layer). These results suggest that enhancement of PKC activity and/or translocation of the enzyme play an important role in the postischemic modulation of synaptic efficacy in the hippocampal formation and neuronal death of CA1 pyramidal cells.