Effect of internal carotid artery reperfusion in combination with Tenecteplase on clinical scores and hemorrhage in a rabbit embolic stroke model

Abstract

In the present study, we used a modification of the rabbit small clot embolic stroke model (RSCEM), a multiple infarct ischemia model to achieve reperfusion (REP) through the internal carotid artery (ICA) following small clot embolization. We determined if increasing regional cortical blood flow (RCBF) following an embolic stroke is beneficial to neurological outcome. We compared this to cerebral reperfusion induced by the administration of the thrombolytic Tenecteplase (TNK, 1.5 mg/kg, IV bolus) in the presence or absence of REP. In this study, we also measured the incidence of ICH following REP and thrombolytic treatment. Following embolization, RCBF was reduced to 48–55% of baseline. When REP was induced by removal of a CCA ligature, RCBF initially increased to 185% of baseline. REP (P 50 = 1.18 ± 0.43 mg) had no effect on embolization-induced behavior measured 24 h following embolization compared to control (P 50 = 1.01 ± 0.48 mg). However, TNK treatment (2-hours post-embolization) in the absence or presence of REP (initiated 2 h following embolization) significantly ( p < 0.05) increased the group P 50 to 2.92 ± 0.55 mg and 2.42 ± 0.40 mg, respectively. In addition, ICH was increased in the REP (42%, p < 0.05) and REP-TNK (35%, p > 0.05) group compared to either the control group (5.5%) or TNK group (10%). This study show that reperfusion of ICA can increase RCBF following embolization, but this is not associated with improved neurological outcome measured using quantal analysis. However, TNK administration significantly increased behavioral outcome when given 2 h following embolization; an increase that is not affected by combining TNK with REP.