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

The effects of intracarotid thrombolysis with recombinant tissue-plasminoge n activator (rt-PA) on cerebral laser Doppler flow (LDF) and the degree of ischemic injury, as revealed by triphenyltetrazolium chloride (TTC) stainin g, were studied 24 h following cerebral thromboembolism in mice. Thromboemb olization 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 i n 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 inj ection induced a progressive LDF restoration to approximate to 115% of cont rol values after 2 h, and brought about a significant reduction of the infa rct volume (62.3 +/- 42.4 mm(3)). Our results indicate that ischemic injury may be significantly attenuated by intracarotid thrombolysis. However, inj ury is not completely reversed, even if reperfusion is initiated as early a s 15 min after embolization.