Two major isoforms of fibronectin (FN) exist in humans and mice. The predominant isoform, plasma FN, lacks the alternatively-spliced extra domain A (EDA), whereas the cellular isoform of FN contains the EDA and is a major component of the extracellular matrix. FN containing the extra domain A (EDA⁺-FN) is absent in the circulation of healthy humans, but is specifically found in pathological settings including diabetes, atherosclerosis, major trauma or ischemic stroke. In murine studies, we have recently found that EDA⁺-FN promotes thrombosis and inflammation. The project will focus on the mechanism by which extra domain A of FN promotes thrombosis and inflammation following ischemic stroke.