Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat

The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA 1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP–dependent protein kinase, and cyclic GMP–dependent protein kinase, respectively. All test compounds were injected topically into the CA 1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1–10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA 1 pyramidal cell death after ischemia and that the fate of vulnerable CA 1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.