Using Cdh5CreERT2;Cxcl12flox mice, in which Cxcl12 was specifically deleted in BBB endothelial cells, plus a mouse model with Cxcr4-deficient NKp46+ cells, we demonstrated that BBB CXCL12–CXCR4 axis was essential for the influx of NK cells into the stroke lesion. This evidence concerns the gene CXCL12 and stroke disorder.