Abstract
Both Erythropoietin (EPO) and bone marrow stromal cells (BMSCs) have been shown to improve outcome after stroke. EPO may improve outcome after stroke through its actions on blood progenitor cells, angiogenesis, or direct action in the CNS. BMSCs may improve outcome after stroke by regeneration, altering plasticity of viable cells, or prevention of cell death. Sorting out these potential modes of actions for EPO and BMSCs has been difficult using in vivo models of stroke. This study investigated neuroprotection afforded by EPO, BMSCs and the combination of these modalities in mouse hippocampal slice cultures after oxygen glucose deprivation (OGD). Significant neuroprotection was observed following post-injury treatment of slice cultures with BMSCs and neuroprotection was augmented by treating BMSCs with EPO. EPO alone did not protect neurons from OGD when given after injury, but was effective when given prior to OGD. The failure of EPO to protect when given after injury did not appear to result from its inability to activate EPO signaling pathways involving phosphorylation of Akt. This study supports the implication that BMSCs may rescue dying neurons after ischemia by providing trophic support. The data also show that EPO’s actions as a neuroprotective agent following stroke may be mediated by its actions on BMSCs.
