Rivaroxaban Promotes Reduction of Embolus Size within Cerebrocortical Microvessels in a Mouse Model of Embolic Stroke.

Abstract

Previous reports have suggested that direct oral anticoagulants exert a prothrombolytic effect against intracardiac thrombi. We hypothesized that these anticoagulants may also help recanalize occluded intracranial arteries via prothrombolytic effects. In this study, we evaluated the effects of rivaroxaban, a direct oral anticoagulant, on fibrin emboli within the cerebrocortical microvessels in a mouse model of embolic stroke. Fibrin emboli prepared ex vivo were injected into the common carotid artery of male C57BL/6 mice, and embolization in the microvessels on the brain surface was observed through a cranial window. Oral administration of rivaroxaban was initiated a week before injection of the emboli. The number and sizes of the emboli were measured at two time points: immediately after and 3 h after the embolus injection in the rivaroxaban-treated mice (n =6) and untreated mice (n =7). The rates of recanalization and change in the embolus size were analyzed between the two groups. Complete recanalization was observed only in the rivaroxaban group (three mice in the rivaroxaban group compared with none in the control group). A significantly higher rate of reduction of the embolus size was observed in the rivaroxaban group than in the control group (P=0.0216). No significant differences between the two groups were observed in the serum levels of the following coagulation markers: thrombin-antithrombin III complexes, D-dimers, or plasmin-α2-plasmin inhibitor complex. Our findings indicate that rivaroxaban may promote reduction in the size of stagnated fibrin emboli in cerebrocortical microvessels in cases of embolic stroke.