Pharmacological investigation for mechanisms of cerebral hemorrhage induced by anti-thrombotic agents

脑出血与抗栓和溶栓治疗急性脑卒中是一个主要的临床问题。我们研究了内源性tPA和MMPs在肝素相关出血性脑梗死中的作用。我们证明了肝素给药引起WT脑出血，但在KO中没有。肝素给药增加WT中tPA活性及其mRNA表达。我们还观察到了诱导MMP 9及其mRNA表达肝素管理WT，但在KO。我们的研究结果表明，内源性tPA通过MMP 9诱导和激活在肝素引起的脑出血中起着重要作用。

Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke is a major clinical problem. We investigated the roles of endogenous tPA and MMPs in hemorrhagic cerebral infarction associated with heparin. We demonstrated that heparin administration caused cerebral hemorrhage in WT but not in KO. Heparin administration increased tPA activity and its mRNA expression in WT. We also observed an induction of MMP9 and its mRNA expression by heparin administration in WT but not in KO. Our findings suggest that endogenous tPA plays an important role in heparin-produced cerebral hemorrhage via MMP9 induction and activation.