Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
Sci Rep. 2018 May 9;8(1):7408. doi: 10.1038/s41598-018-25820-y.
Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.
新型抗凝剂在糖尿病性缺血性卒中（IS）患者血管内血栓切除术（ET）中的管理颇具挑战性，因为可能会增加脑出血风险。本研究评估了 Rivaroxaban 治疗的糖尿病大鼠 ET 后出血性转化（HT）风险增加的情况。雄性 Sprague-Dawley 大鼠通过腹腔注射 60mg/kg 链脲佐菌素诱导糖尿病。4 周后，大鼠口服给予 30mg/kg Rivaroxaban/生理盐水预处理；监测凝血酶原时间。1 小时后通过线诱导短暂性大脑中动脉闭塞（tMCAO）诱导 IS 和 ET，tMCAO 模拟机械性 ET 治疗近端 MCA 闭塞，60 分钟后闭塞。再灌注 24 小时后，测量梗死体积、HT、血脑屏障（BBB）通透性、缺血性损伤周围紧密连接和基质金属蛋白酶-9（MMP-9）活性。与正常大鼠相比，糖尿病大鼠在 ET 后 24 小时似乎表现出更高的梗死体积和 HT。Rivaroxaban 组与糖尿病对照组的梗死体积和功能结果无差异。未检测到 Rivaroxaban 治疗下 HT 体积和 BBB 通透性的显著增加。与糖尿病对照组相比，Rivaroxaban 组的闭合蛋白表达没有明显降低，MMP-9 活性也没有升高。总之，在 Rivaroxaban 治疗下，Rivaroxaban 并未增加近端 MCA 闭塞糖尿病大鼠 ET 后的 HT，因为 Rivaroxaban 对缺血后 BBB 通透性的影响较小。
