Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus

Apoptosis plays an important role in delayed neuronal cell death after cere bral ischemia. Activation of Akt/protein kinase B has been recently reporte d to prevent apoptosis in several cell types. In this article the authors e xamine whether induction of ischemic tolerance resulting from a sublethal i schemic insult requires Akt activation. Sublethal ischemia gradually and pe rsistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Se r-473 showed no obvious decrease in preconditioned gerbils but a marked dec rease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation wer e correlated with changes in Akt activities, as measured by an in vitro kin ase assay. Intracerebral ventricular infusion of wortmannin before precondi tioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose- dependent manner and the neuroprotective action of preconditioning. These r esults suggest that Akt activation is induced by a sublethal ischemic insul t in gerbil hippocampus and contributes to neuroprotective ischemic toleran ce in CAI pyramidal neurons.