The role of extracellular signal-regulated kinases in the neuroprotection of limb ischemic preconditioning.

To clarify the role of phosphorylated extracellular signal-regulated kinases (pERK1/2) in the neuroprotection of limb ischemic preconditioning (LIP) in rats, we investigated the expression of pERK1/2 using Western blot and flow cytometry in the hippocampus after LIP and the effect of pERK1/2 inhibitor PD 98059 on the neuroprotection of LIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by severe ischemic insult. It demonstrated that pERK1/2 in the hippocampus increased after LIP. In the CA1 hippocampus, ERK1/2 activation began to increase at 6h and reached peak at 12h after LIP, and decreased to sham level at 5d after LIP. On the other hand, in the CA3/DG, pERK1/2 enhanced at 1d, reached peak at 3d, and lasted to 5d after LIP. Pretreatment with PD 98059 before LIP blocked the neuroprotection of LIP in a dose-dependent manner. These findings supported that the upregulation of pERK1/2 in the CA1 hippocampus contributed to the neuroprotection of LIP against DND normally caused by the brain ischemic insult.