Hyperfibrinolysis induces BBB leakage in a plasmin-dependent manner. (A) Design of the experiments performed to study BBB permeability, using NIRF techniques. EB extravasation was measured 48 hours after pLIVE (0, wild-type or mutated tPA plasmids) hydrodynamic transfection in the brain and the spinal cord. (B) All pLIVE-tPA constructions (wild-type and tPA mutations in Finger [Δ-Finger] and Kringle-2 [K2*] domains) promoted EB extravasation in the brain compared with pLIVE-0 (control). (C) Normalized mean fluorescence quantification of B (n = 5 per group). (D) BBB leakage is dependent on plasmin generation, as inhibition of the activation of plasminogen into plasmin (by EACA and tranexamic) or inhibition of plasmin activity (by aprotinin) prevented EB extravasation in mice with hyperfibrinolysis. *P < .05 vs control.