Intravenous tenecteplase bridging reperfusion ameliorates cerebral ischemia/reperfusion injury by improving microvascular circulation in rats.

IF 5.5 2区医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2025-01-16 DOI:10.1016/j.jtha.2024.12.042

Yue-Xin Ning, Ji-Ru Cai, Ting-Ting Wang, Yi-Han Wang, Yu Cui, Hui-Sheng Chen

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Abstract

Background: Endovascular thrombectomy (EVT) alone was not demonstrated to be noninferior to intravenous alteplase bridging EVT in acute large vessel occlusion stroke. Using the cerebral ischemia/reperfusion (I/R) injury model, intravenous tenecteplase (TNK) was administrated after ischemia, followed by reperfusion at various time points.

Objectives: To investigate whether intravenous TNK bridging EVT vs EVT alone could improve I/R injury, and this effect may be associated with the time from TNK to reperfusion.

Methods: Rats received intravenous TNK (1.4 mg/kg) or vehicle (sterile water) 1.0 hours after middle cerebral artery occlusion, followed by reperfusion after 0.5 or 1.0 hours following TNK. Neurological deficit scores, infarct volume, and brain edema were measured 24 hours after middle cerebral artery occlusion. Microthrombi were determined by immunofluorescence staining for CD31⁺/fibrinogen⁺ and CD31⁺/thrombocyte⁺. Inflammatory cell infiltration in the ischemic brain region was determined by flow cytometry.

Results: Compared with vehicle, TNK significantly reduced neurological deficit scores, brain infarction, neuroinflammation, and blood-brain barrier disruption, and significantly reduced intravascular fibrin and platelet deposition and brain inflammatory cell infiltration in the penumbra of I/R rats. Furthermore, a better beneficial trend was found in TNK bridging reperfusion at 0.5 hours after TNK compared with TNK bridging reperfusion at 1.0 hours after TNK.

Conclusion: Our results demonstrate that intravenous TNK bridging reperfusion produced neuroprotective action through dissolving microvascular thrombus and alleviating inflammatory cell infiltration to improve microcirculation, with the result of maintaining blood-brain barrier integrity and inhibiting neuroinflammation, and the neuroprotective benefit may be associated with the time from TNK to reperfusion.

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静脉替奈普酶桥接再灌注通过改善微血管循环改善大鼠脑缺血再灌注损伤。

背景：在急性大血管闭塞（LVO）卒中中，单纯血管内治疗（EVT）并不比静脉注射阿替普酶桥接EVT更有效。采用脑缺血再灌注（I/R）损伤模型，在缺血再灌注后不同时间点静脉注射替奈普酶（TNK）。目的：探讨静脉滴注TNK桥接EVT与单独EVT是否能改善I/R损伤，这种作用可能与从TNK到再灌注的时间有关。方法：大鼠大脑中动脉闭塞（MCAO）后1.0 h静脉注射TNK （1.4 mg/kg）或载药（无菌水），TNK后0.5或1.0 h再灌注。在MCAO后24小时测量神经功能缺损评分、梗死体积和脑水肿。采用CD31+/纤维蛋白原+和CD31+/血栓细胞+免疫荧光染色检测微血栓。流式细胞术检测脑缺血区炎症细胞浸润情况。结果：与对照组相比，TNK显著降低I/R大鼠神经功能缺损评分、脑梗死、神经炎症、血脑屏障（BBB）破坏，显著降低血管内纤维蛋白、血小板沉积、半暗区脑炎性细胞浸润。此外，与TNK后1.0小时的TNK桥接再灌注相比，TNK后0.5小时的TNK桥接再灌注有更好的有益趋势。结论：我们的研究结果表明，静脉内TNK桥接再灌注通过溶解微血管血栓，减轻炎症细胞浸润，改善微循环，维持血脑屏障完整性，抑制神经炎症，从而产生神经保护作用，其神经保护作用可能与TNK至再灌注的时间有关。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.