Focal embolic cerebral ischemia in the rat

In this model, the middle cerebral artery (MCA) is occluded with a fibrin-rich allogeneic clot, producing an embolic model of MCA occlusion in the rat that mimics the key components of neurovascular damage observed in human ischemic stroke. Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 h of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we previously developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. Here we describe in detail the surgical procedures of our model, including preparing emboli from rat donors. These procedures can be typically completed within ∼30 min, and they are highly adaptable to other strains of rats, as well as mice, in both sexes. Thus, this model provides a powerful tool for translational stroke research.