Icariin and mesenchymal stem cells synergistically promote angiogenesis and neurogenesis after cerebral ischemia via PI3K and ERK1/2 pathways

Mesenchymal stem cells (MSCs) are one promising candidate for regenerative therapy of ischaemic stroke through transdifferetiation and paracrine actions. Icariin (ICA) has shown great potential in improving cell activity and VEGF, BDNF secretion in vitro. Whether they will synergistically improve therapy effect on cerebral ischemia is unknown. In this study, male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion and ICA/MSC treatment. Results showed that ICA and MSCs combined treatment greatly reduced brain infarction volume, improved neurologic deficits of motor and somatosensory function and neurobehavioral outcomes. The combined therapy increased expression of VEGF and BDNF to a maximum through activating PI3K and ERK1/2 pathways in the hippocampus and frontal cortex in response to transient MCAO. They notably promoted angiogenesis and neurogenesis in vivo. Thus, ICA and MSCs combined treatment may represent a feasible approach for improving the beneficial effects of stem cell therapy for cerebral ischemia.