Hemorrhagic transformation in a thrombolysis animal model

초록

Background : Thrombolytic therapy, the approved treatment of acute ischemic stroke, has major shortcomings of hemorrhagic transformation, still limiting wide clinical application. Appropriate animal model will help to elucidate the mechanism. We thus tried to develop thrombolysis animal model which has similar pathophysiology with human stroke, and also find the condition of hemorrhagic transformation. Methods : In male wistar rats, focal embolic occlusion of proximal middle cerebral artery (MCA) was made by injection of microclot into modified microcatheter. After 1,6, and 24 hours respectively, each group of rats (n=15) were infused 10mg/kg of recombinant tissue plasminogen activator (rTPA) intravenously for 30 minutes. Decapitation and TTC staining was done 24 hours after thrombolysis. Results : Infarct size was smallest in 1 hour rTPA group (4.2+3.3% of contralateral hemisphere) indicating successful thrombolytic reperfusion, and largest in 24 hour rTPA group (26.4+12.9%). Hemorrhagic transformation was noticed in 2, 2, and 7 rats in 1, 6, and 24 hour group respectively, and the pattern was mostly intracerebral hemorrhage in the caudato-putamen area, rare in the cortex. Conclusions : Our animal model of local embolism and thrombolysis has similar mechanism and characteristics to clinical thrombolytic therapy including hemorrhagic transformation, directly applicable to future thrombolysis research.