Effects of ML351 and tissue plasminogen activator combination therapy in a rat model of focal embolic stroke

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by risks of hemorrhagic transformation (HT). We have reported that a new 12/15-lipoxygenase (12/15-LOX) inhibitor ML351 reduced tPA related HT in mice subjected to experimental under anticoagulation. In this study, we asked whether can ameliorate induced an embolic model. Rats were middle cerebral artery occlusion 2 or 3 hr ischemia and infusion, without ML351. Regional blood flow was monitored after continuously for 1 treatment determining reperfusion. Hemoglobin determined brain homogenates infarct volume quantified at 24 stroke.12/15-LOX, cluster differentiation 68(CD68), immunoglobulin G (IgG), tight junction proteins expression detected immunohistochemistry. significantly hemorrhage affecting its thrombolytic efficacy. also blood–brain barrier disruption improved preservation proteins. combination neurological deficit rats even though did not further reduce the compared alone treated animals. Pro-inflammatory cytokines suppressed both vivo vitro experiments. showed c-Jun-N-terminal kinase (JNK) brains microglia cultures, whereas exogenous 12-HETE attenuated effect vitro. conclusion, beneficial ameliorating ischemic stroke. This protective probably because 12/15-LOX inhibition suppression JNK-mediated microglia/macrophage activation.