Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat

Abstract

We report the technical details and validation of an improved rat model for thromboembolic stroke and rt-PA induced reperfusion, which closely resembles clinical embolic stroke. The middle cerebral artery (MCA) was proximally occluded by injection of twelve medium sized (1.5 x 0.35 mm), fibrin-rich autologous blood clots. On inspection, densely packed clot material was found at the ipsilateral MCA origin in all untreated animals. Autoradiographic rCBF measurements showed severe ischemic deficit throughout the ipsilateral MCA territory in untreated animals. The volume in which flow values fell below 30 ml/100 g per min was 54 +/- 14% of the hemispheric volume. In all rt-PA treated animals the proximal MCA was recanalised, and the volume with flow values below 30 ml/100 g per min was reduced to 29 +/- 17%. Histological findings paralleled the spatial spread of the CBF deficit. The rat model presented is well-suited for investigations of the specific pathophysiology of thromboembolic stroke. Furthermore it allows detailed studies of thrombolytically induced reperfusion, beyond the question of successful recanalisation.