EPO and brain ischemia: This complex activates the transcription of target genes, such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF).98 EPO is known as an effective agent against ischemic injury, particularly in cardiac, renal, and neural protection, through activating several protective signaling pathways.99 VEGF also plays a role in angiogenesis and neurotrophic processes by increasing vascular density and blood flow.3, 100 As such, cerebral ischemia injury could be significantly reduced following hypoxic conditioning due to the increased expression of HIF-1 and its target genes.