Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model.

Abstract

Background and Purpose: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model.Methods: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured.Results: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p=0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p=0.007) and increased the survival rate from 0.48 to 0.96 (p=0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed.Conclusions: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model. (Stroke 1992;23:1167-1174 KEY WORDS • cerebral blood flow • cerebral ischemia • thrombolytic therapy • rats

Adjuvant Treatment With Neuroserpin Increases the Therapeutic Window for Tissue-Type Plasminogen Activator Administration in a Rat Model of Embolic Stroke

“…2,9,15,16 Recent data obtained from tPA-deficient mice indicate that tPA may and perfusion-weighted (E through H) MRI of representative rats treated with neuroserpin in combination with tPA (A, B, E, and F) or tPA alone (C, D, G, and H). Reduction in CBF (A and C) and ischemic lesion (E and G) were detected in the ipsilateral MCAsupplied territory in the rat treated with neuroserpin in combination with tPA (A and E) or with tPA (C and G) before treatment.…”

Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in Rats

“…[11][12][13] Considerable experimental evidence with the use of thrombolytic agents in animal stroke models has shown that autologous clots can be effectively lysed by thrombolytics and that functional neurological recovery results. 16,17 In the present study we used a novel soluble recombinant form of human CD39 with potent ADPase and ATPase activities and strong inhibitory effects on platelet aggregation. 7 In in vitro studies, solCD39 blocks ADP-induced human platelet aggregation and inhibits collagen and thrombin receptor agonist peptideinduced platelet reactivity.…”

Effect of Delayed Thrombolysis with rt-PA in a Rat Embolic Stroke Model

“…Lyden et al (1989) and Del Zoppo et al (1990) found a similar frequency of hemorrhagic transfor mation of infarctions in rabbit and baboon stroke models regardless of whether the thrombolysis was started 90 or 180 min after induction of ischemia. In our laboratory, we found a significant effect of thrombolysis on clinical recovery, mortality, infarct size, and edema development in three different em bolic stroke rat models (Overgaard et al, 1992a(Overgaard et al, , 1993) when rt-PA was administered 15 min after embolization with almost no hemorrhagic complica tions.…”