Recombinant tissue plasminogen activator reduces infarct size after reversible thread occlusion of middle cerebral artery in mice.

It has been suggested that tissue plasminogen activator (tPA), which is widely used for the thrombolytic treatment of stroke, exhibits neurotoxic side effects. To test this hypothesis, mice exposed to 90 min nonthrombotic middle cerebral artery thread occlusion were treated with 10 mg/kg recombinant tPA (rt-PA) at 15 min after the onset of vascular occlusion. Measurements of blood flow, infarct volume, brain swelling and neurological performance revealed faster recirculation and a significant reduction of ischemic injury in rt-PA-treated animals. These data are at variance with previous reports on tPA neurotoxicity and demonstrate, on the contrary, that tPA protects the brain even after non-thrombotic vascular occlusion.