Activation of p21WAF1/CIP1 by erythropoietin prevents neuronal cell death and mediates ischemic preconditioning in primary cortical neurons

Rational: Ischemic preconditioning (IP) triggers adaptive mechanisms in tissues or isolated cells and induces tolerance against an otherwise lethal ischemia. Gene expression profiling revealed an upregulation of the cell cycle inhibitor p21WAF1/CIP1 (p21) on mRNA-level following IP in rat primary cortical neurons and mouse brains. In previous studies we have identified erythropoietin (EPO) as an essential mediator of IP conferring neuroprotection via a PI3K/Akt dependent pathway. The aim of the present study is to elucidate the functional role of p21 in IP mediated by EPO. Methods and Results: Primary cortical n…