Novel combination therapy of recombinant annexin 2 and low dose recombinant tissue plasminogen activator in embolic rat stroke model: A magnetic resonance imaging study

Introduction. In the treatment of acute phase ischemic stroke, tPA has high risk of hemorrhage which is usually fatal, and the treatment time window is very narrow. Therefore, the search for alternatives to tPA that can reduce hemorrhagic risk and lengthen treatment time window is an urgent priority. The recent studies report recombinant annexin 2 (rAN2) amplifies tPA converted plasmin generation in vitro (1), and suggest rAN2 as an alternative novel fibrinolytic agent with a significantly lower rate of hemorrhagic transformation (2). The ability to visualize ischemic tissue status longitudinally by MRI could provide vital data for understanding drug action on different ischemic tissue types, determining the optimal treatment time window, and improving experimental designs to reach the maximum efficacy, and avoiding fatal hemorrhagic transformation. In this study, we hypothesized the combination therapy of tPA and rAN2 reduces infarct size and significantly lowers the risk of hemorrhagic transformation.