Intravenous injection of neural progenitor cells facilitates angiogenesis after cerebral ischemia

Earlier we demonstrated that the injection of neural progenitor cells ( NPC s) has therapeutic potential for the improvement of learning dysfunction after cerebral ischemia. However, it remained to be clarified how transplantation of NPC s can improve ischemia‐induced dysfunction. In this study, we examined whether intravenous injection of NPC s after cerebral ischemia could enhance angiogenesis by affecting the expression of angiogenic factors. The injection of NPC s on day 7 after cerebral ischemia enhanced angiogenesis on day 28. Vascular endothelial growth factor ( VEGF ) and its receptor VEGFR 2 were increased in expression by the NPC injection. The level of angiopoietin‐1 ( A ng‐1), an angiogenic factor, but not that of A ng‐2, which acts as an antagonist for the A ng‐1 receptor, was also increased on day 28. In addition, the expression of A ng‐1 receptor T ie2 was enhanced in brain capillaries. Furthermore, the amounts of tight junctional proteins, which are in the blood–brain barrier and whose expression occurs downstream of A ng‐1/ T ie2 signaling, were increased by the NPC injection. These results suggest that the NPC injection promoted angiogenesis through A ng‐1/ T ie2 and/or VEGF / VEGFR 2 signaling in brain capillaries after cerebral ischemia. Such signaling might have the potential for causing vascular stabilization and maturation for a long period after cerebral ischemia.