Aggravation of focal cerebral ischemia by tissue-plasminogen activator is reversed by rosuvastatin – role of endothelial NO synthase

Background: It has been proposed that the thrombolytic tissue-plasminogen activator (t-PA) may aggravate ischemic injury after stroke via secondary hemodynamic disturbances. The underlying mechanisms, however, are unclear. To elucidate this issue, we examined the effects of t-PA, administered either alone or in combination with rosuvastatin, on focal ischemic brain injury, intracellular signaling and endothelial NO synthase (eNOS) expression. Methods and Results: Mice were subjected to transient (90 minutes) intraluminal middle cerebral artery (MCA) occlusions. t-PA treatment initiated immediately after ischemia…