Recombinant tissue-plasminogen activator-induced thrombolysis after cerebral thromboembolism in mice

The effects of intracarotid thrombolysis with recombinant tissue-plasminogen activator (rt-PA) on cerebral laser Doppler flow (LDF) and the degree of ischemic injury, as revealed by triphenyltetrazolium chloride (TTC) staining, were studied 24 h following cerebral thromboembolism in mice. Thromboembolization with fibrin-rich clot material (0.28-mu l clot volume) led to an LDF decline to about 20-30% of baseline in untreated mice, which resulted in reproducible infarcts of the middle cerebral artery (MCA) territory (122.8 +/- 29.4 mm(3)). Administration of rt-PA (10 mg/kg) 15 min after clot injection induced a progressive LDF restoration to approximate to 115% of control values after 2 h, and brought about a significant reduction of the infarct volume (62.3 +/- 42.4 mm(3)). Our results indicate that ischemic injury may be significantly attenuated by intracarotid thrombolysis. However, injury is not completely reversed, even if reperfusion is initiated as early as 15 min after embolization.