PDF(Pubmed)
Abstract：
Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key component of the KKS - in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.
摘要：
激肽释放酶-激肽系统的激活促进血管渗漏，炎症,和缺血性中风的神经变性。据报道，在缺血性卒中急性期抑制血浆激肽释放酶（PK）-KKS的关键成分可减少血栓形成。炎症,以及血脑屏障的损伤.然而,PK在脑缺血后恢复期的作用尚不清楚.为此,我们评估了从第3天开始抑制亚急性PK对短暂性中动脉闭塞(tMCAO)后恢复过程的影响.我们的研究证明了PK抑制在tMCAO后第7天通过减少梗死体积和改善功能结果的保护作用。此外,我们观察到脑微血管血栓形成减少，较少浸润的免疫细胞，以及血脑屏障完整性的改善。通过促进紧密连接的重新融合，促进了这种保护作用，减少有害的基质金属蛋白酶，并上调再生血管生成标志物。我们的发现表明，亚急性期的PK抑制可能是加速卒中后恢复过程的有希望的方法。
