Our key findings demonstrate that (1) plasma BDNF levels are significantly reduced in AIS patients with T2DM compared to nondiabetic AIS patients and healthy controls; (2) reduced BDNF correlates with higher fibrin density, lower thrombus permeability, and increased stroke severity (NIHSS); (3) in vitro supplementation of rHu-BDNF restores physiological clot morphology by reducing fibrin density, prolonging clotting time, and enhancing fibrinolysis. This evidence concerns the gene BDNF and Stroke.