Post-ischemic activation of protein kinase C epsilon protects the hippocampus from cerebral ischemic injury via alterations in cerebral blood flow

Protein kinase C(PKC) is a family of serine/threonine-isozymes that are involved in many signaling events in normal and disease states. Previous studies from our lab have demonstrated that epsilon PKC plays a pivotal role in neuroprotection induced by ischemic preconditioning. However, the role of epsilon PKC during and after brain ischemia is not clearly defined. Therefore, in the present study, we tested the hypothesis that activation of epsilon PKC during an ischemic event is neuroprotective. Furthermore, other studies have demonstrated that epsilon PKC mediates cerebral ischemic tolerance in the rat brain by decreasing vascular tone. Thus, we also tested the effects of epsilon PKC activation during ischemia on cerebral blood flow (CBF). We found that psi epsilon-Receptors for Activated C Kinase (RACK), a epsilon PKC-selective peptide activator, injected intravenously 30 min before induction of global cerebral ischemia conferred neuroprotection in the CA1 region of the rat hippocampus. Moreover, measurements of CBF before, during, and after cerebral ischemia revealed a significant reduction in the reperfusion phase of rats pretreated with psi epsilon RACK as compared to Tat peptide (vehicle). Our results suggest that epsilon PKC can protect the rat brain against ischemic damage by regulating CBF. Thus, epsilon PKC may be one of the treatment modalities against ischemic injury. (C) 2010 Elsevier Ireland Ltd. All rights reserved.