The clot thickens--thrombolysis and combination therapies.

Stroke in the human is most frequently caused by an intra-arterial clot. In order to investigate human stroke, appropriate and relevant animal models must be selected. Since the only approved treatment of stroke is that of recombinant tissue plasminogen activator (rtPA) the models selected should be amenable to thrombolytic treatment. We therefore describe a new model of embolic stroke in the rat in which a fibrin rich clot is placed via the internal carotid artery (ICA) at the origin of the middle cerebral artery (MCA). Data are summarized describing treatment of embolic stroke with rtPA administered at various times after stroke, the use of combination antiadhesion molecule and rtPA therapy, and the application of MRI to monitor the temporal evolution of physiological changes within ischemic tissue with and without rtPA intervention and to predict therapeutic efficacy.