Erythropoietin induces synaptogenesis and neurite repair after hypoxia ischemia-mediated brain injury in neonatal rats.

The memory dysfunction is one of the disastrous outcomes for perinatal hypoxia ischemia. Erythropoietin (EPO) has been demonstrated as a neuroprotective agent with multiple effects in a series of neurological diseases. We hypothesized that disruption of neural network including synapses and neurites would contribute to memory dysfunction induced by hypoxia ischemia. The aim of the present study was to elucidate the involvement of EPO on synaptogenesis and neurite repair following perinatal hypoxia ischemia. Using a neonatal hypoxia ischemia rat model, we found that EPO rescued hypoxia ischemia-induced decrease of synaptic proteins including Synapsin1 and PSD95 rather than GluR1 in the cortex and hippocampus. In addition, EPO reduced the expression of APP (an axonal injury marker), induced the expression of microtubule-associated protein MAP-2 (a dendritic marker), and restored axonal density after hypoxia ischemia. These changes contributed to improving electrophysiological properties of synapses and spatial memory performance. In summary, our data revealed an important role of EPO in synaptogenesis and neurite repair, providing a new insight into cellular mechanisms underlying cognitive and memory dysfunction associated with perinatal hypoxia ischemia.