阿斯帕拉金内酶抑制减弱组织等离子素激活剂诱导的脑出血变化在缺血性中风后
Guanfeng Xie1, Gege Jiang1, Liqin Huang1
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
CNS neuroscience & therapeutics
|March 21, 2025
概括
阿斯巴拉金内酶 (AEP) 在缺血性中风中延迟组织等离子素激活剂 (tPA) 治疗后恶化出血转化. 用R13抑制AEP可能会提高tPA的安全性和有效性.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 组织等离子素激活剂 (tPA) 是一种已批准的治疗急性缺血性中风的疗法.
- tPA的使用受到出血转化 (HT) 和狭窄的治疗窗口的限制.
- 阿斯巴拉金内酶 (AEP) 导致神经元死亡,但其在HT中的作用尚不清楚.
研究的目的:
- 为了研究AEP在延迟tPA在缺血性中风中给予后的出血转化 (HT) 中的作用.
- 为了评估R13的治疗潜力,一个TrkB激动剂和AEP抑制剂,在缓解tPA诱导的HT.
主要方法:
- 中脑动脉封闭/再输 (MCAO/R) 模型在野生类型和AEP淘汰赛小鼠中,推迟tPA给药.
- 评估心脏病发作体积,神经功能,BBB完整性标记 (埃文斯蓝色泄漏,接口蛋白) 和MMP/LRP-1表达.
- 在实验室模型中,使用氧气-葡萄糖剥夺 (OGD) 在用tPA和AEP抑制剂7,8-二氧黄 (7,8-DHF) 治疗的HUVEC中.
主要成果:
- 与野生型小鼠相比,用tPA治疗的AEP淘汰小鼠表现出减少了心脏病发作量,改善了神经功能,并保持了BBB完整性.
- 在tPA治疗小鼠中,R13治疗保护了BBB,并降低了MMP2,MMP9和LRP-1表达.
- 在体外,7,8-DHF改善了内皮细胞连接蛋白,抑制了MMP2,MMP9和LRP-1水平.
结论:
- 在缺血性中风中推迟tPA治疗后,AEP通过通过LRP-1,MMP2和MMP9激活来破坏BBB完整性,从而加剧HT.
- R13显示出作为一种预防性治疗来减少tPA诱导的HT的潜力.
- 抑制AEP是一种有前途的策略,可以提高因缺血性中风延迟tPA血栓溶解的安全性.
相关概念视频
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
Ischemic Stroke ll: Pathophysiology
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...


