In the present study, combination treatment of stroke showed a significant upregulation of Netrin-1 and Robo-1 levels expression as well as an increase of angiogenesis and neurogenesis in the ischemic brain after stroke, suggesting that axonal guidance signaling might be one of the underlying mechanisms involved in the beneficial effects of the combined actions of XSEC and EE on endogenous repair, e.g., angiogenesis and neurogenesis following cerebral ischemic injury. Here, NTN1 is linked to Stroke.