Erythropoietin's Beta Common Receptor Mediates Neuroprotection in Spinal Cord Neurons

Background. Paraplegia from spinal cord ischemia-reperfusion (SCIR) remains an elusive and devastating complication of complex aortic operations. Erythropoietin (EPO) attenuates this injury in models of SCIR. Upregulation of the EPO beta common receptor (beta cR) is associated with reduced damage in models of neural injury. The purpose of this study was to examine whether EPO-mediated neuroprotection was dependent on bcR expression. We hypothesized that spinal cord neurons subjected to oxygen-glucose deprivation would mimic SCIR injury in aortic surgery and EPO treatment attenuates this injury in a beta cR-dependent fashion. Methods. Lentiviral vectors with beta cR knockdown sequences were tested on neuron cell cultures. The virus with greatest beta cR knockdown was selected. Spinal cord neurons from perinatal wild-type mice were harvested and cultured to maturity. They were treated with knockdown or nonsense virus and transduced cells were selected. Three groups (beta cR knockdown virus, nonsense control virus, no virus control; n = 8 each) were subjected to 1 hour of oxygen-glucose deprivation. Viability was assessed. beta cR expression was quantified by immunoblot. Results. EPO preserved neuronal viability after oxygen-glucose deprivation (0.82 +/- 0.04 versus 0.61 +/- 0.01; p < 0.01). Additionally, EPO-mediated neuron preservation was similar in the nonsense virus and control mice (0.82 +/- 0.04 versus 0.80 +/- 0.05; p = 0.77). EPO neuron preservation was lost in beta cR knockdown mice compared with nonsense control mice (0.46 +/- 0.03 versus 0.80 +/- 0.05; p < 0.01). Conclusions. EPO attenuates neuronal loss after oxygen-glucose deprivation in a beta cR-dependent fashion. This receptor holds immense clinical promise as a target for pharmacotherapies treating spinal cord ischemic injury. (C) 2017 by The Society of Thoracic Surgeons