In conclusion, citicoline induces angiogenesis and improves survival of human brain microvessel endothelial cells through pathways involving p-ERK1/2, and IRS-1 and it is probable that other novel signalling intermediates are also involved including Histone H2B and HER2 (more studies are needed to confirm this) and therefore following chronic treatment, its beneficial effects after stroke may in part be due to revascularization. Here, IRS1 is linked to Stroke.