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

Vascular endothelial growth factor receptor I (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 I is also expressed in monocytes and macrophages; mice lacking the VEGFR-I 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-I 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-I TK-/- myeloid cells into the infarcted tissue and reduced postischemic angiogenesis at 3 days 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-I signaling in the early regulation of BM infiltration and angiogenesis after brain ischemia.