FLT4 and ischemic stroke: In this proof-of-concept study, we use rat and mouse models of focal cerebral ischemia along with co-cultures of lymphatic endothelium and macrophages to show that (a) VEGF-C/VEGFR3 signaling activates lymphatic endothelium in CLNs after ischemic stroke, and (b) pharmacological blockade of VEGFR3 signaling or surgical removal of superficial CLNs ameliorates post-stroke inflammation and reduces brain injury.