Intravenous injection of neural progenitor cells facilitates angiogenesis after cerebral ischemia
Article first published online: 28 DEC 2012
© 2012 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Brain and Behavior
Volume 3, Issue 2, pages 43–53, March 2013
How to Cite
Moriyama, Y., Takagi, N., Hashimura, K., Itokawa, C. and Tanonaka, K. (2013), Intravenous injection of neural progenitor cells facilitates angiogenesis after cerebral ischemia. Brain and Behavior, 3: 43–53. doi: 10.1002/brb3.113
- Issue published online: 14 MAR 2013
- Article first published online: 28 DEC 2012
- Manuscript Accepted: 26 NOV 2012
- Manuscript Revised: 19 NOV 2012
- Manuscript Received: 18 OCT 2012
- Takeda Science Foundation
- cerebral ischemia;
- neural progenitor cells;
- tight junctional protein;
Earlier we demonstrated that the injection of neural progenitor cells (NPCs) has therapeutic potential for the improvement of learning dysfunction after cerebral ischemia. However, it remained to be clarified how transplantation of NPCs can improve ischemia-induced dysfunction. In this study, we examined whether intravenous injection of NPCs after cerebral ischemia could enhance angiogenesis by affecting the expression of angiogenic factors. The injection of NPCs on day 7 after cerebral ischemia enhanced angiogenesis on day 28. Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 were increased in expression by the NPC injection. The level of angiopoietin-1 (Ang-1), an angiogenic factor, but not that of Ang-2, which acts as an antagonist for the Ang-1 receptor, was also increased on day 28. In addition, the expression of Ang-1 receptor Tie2 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 Ang-1/Tie2 signaling, were increased by the NPC injection. These results suggest that the NPC injection promoted angiogenesis through Ang-1/Tie2 and/or VEGF/VEGFR2 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.