Plasminogen activator inhibitor-1 augments damage by impairing fibrinolysis after traumatic brain injury.

ABSTRACT:

Objective

Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma.

Methods

We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation by tranexamic acid, and we confirmed our results in PAI-1-deficient animals.

Results

SUBMITTER: Griemert EV 

PROVIDER: S-EPMC6593843 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature