Skip Navigation LinksHome > February 2010 - Volume 69 - Issue 2 > VEGFR-1 Signaling Regulates the Homing of Bone Marrow-Derive...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e3181c9c05b
Original Articles

VEGFR-1 Signaling Regulates the Homing of Bone Marrow-Derived Cells in a Mouse Stroke Model

Beck, Heike DVM; Raab, Sabine PhD; Copanaki, Ekaterini PhD; Heil, Matthias PhD; Scholz, Alexander; Shibuya, Masabumi MD, PhD; Deller, Thomas MD, PhD; Machein, Marcia MD, PhD; Plate, Karl H. MD, PhD

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Abstract

Vascular endothelial growth factor receptor 1 (VEGFR-1) is highly expressed in endothelial cells and regulates developmental angiogenesis by acting as a decoy receptor and trapping VEGF-A. Vascular endothelial growth factor receptor 1 is also expressed in monocytes and macrophages; mice lacking the VEGFR-1 tyrosine kinase (TK) domain (VEGFR-1 TK−/− mice) display impaired macrophage function. Because macrophages are recruited to sites of cerebral ischemic infarcts, we hypothesized that lack of VEGFR-1 TK in bone marrow(BM) cells would affect the outcome in an experimental stroke model. We performed BM transplantation experiments in C57BL/6J mice using VEGFR-1 TK+/+ and VEGFR-1 TK−/− mice as BM donors and analyzed cell infiltration after cerebral ischemia. There was reduced initial recruitment of VEGFR-1 TK−/− myeloid cells into the infarcted tissue and reduced postischemic angiogenesis at 3days postischemia. By 10 days, the numbers of infiltrating cells and the densities of vessels in the infarct peri-infarct zone were similar for both groups. Neither infarct size at 3 and 10 days postischemia nor neurological performance at 24 hours was different between the experimental groups. These results support a role of VEGFR-1 signaling in the early regulation of BM infiltration and angiogenesis after brain ischemia.

© 2010 American Association of Neuropathologists, Inc

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