血管新生是缺血性脑卒中后损伤修复的重要机制，但是缺乏有效的调控手段。我们前期研究证明，重组ADAMTS13可降低急性脑缺血后溶栓引起的脑出血，并减轻脑水肿。我们近期在预实验中发现，Adamts13-/-小鼠在脑缺血后血管新生和内皮细胞增殖方面存在明显缺陷，并且其血管灌注能力下降，血管渗漏加重。综合国内外最新研究进展，本项目拟以ADAMTS13在脑缺血后新生血管形成、成熟和功能重塑中的作用为主线，运用基因敲除、重组蛋白、多光子显微镜活体动物脑血管成像、分子生物学以及行为学检测等手段，阐明ADAMTS13通过VWF及其内皮细胞配体和pVEGFR-2/Tie2途径，调控脑缺血后血管新生和功能重塑的关键环节和作用机制，发现和鉴定新的重要调控分子，并从转化应用的角度，探索重组ADAMTS13促进脑缺血后血管新生-神经再生-损伤修复的新策略，为缺血性脑卒中后神经功能障碍的治疗提供新的视点和理论基础。

Although the angiogenic response may be functionally important for brain repair after ischemic stroke, therapeutic options for promoting angiogenesis remain limited. The von Willebrand factor (VWF)–cleaving protease ADAMTS13 was shown to play a pivotal role after acute stroke. Recently, we have reported that recombinant ADAMTS13 (r-ADAMTS13) reduced tPA-related cerebral hemorrhage after acute ischemic stroke. Furthermore, we demonstrated that r-ADAMTS13 attenuated brain injury after intracerebral hemorrhage. However, the role of ADAMTS13 in angiogenesis after stroke is unknown. Our preliminary data show that Adamts13-/- mice had significant reduction in neovascularization and proliferation of endothelial cells at 14 days after ischemic stroke. These were accompanied by decreased brain capillary perfusion and increased vascular permeability. In this project, we will further assess the effects and mechanism of ADAMTS13 on formation, maturation, remodeling and function of the newly formed capillary after ischemic stroke. We will employ mouse stroke model, using Adamts13-/- and Adamts13-/- vwf/- mice, r-ADAMTS13, multi-photon microscopy, molecular biological and behavior analysis approaches to determine whether VWF and its ligands in endothelial cells as well as pVEGFR-2/Tie2 are involved in the effects of ADAMTS13 on neovascularization and vascular remodeling following ischemic stroke. We will also determine the effects of r-ADAMTS13 on angiogenesis, neurogenesis and functional recovery after ischemic stroke. These proposed studies may provide novel insights into improving post-stroke vascular remodeling and brain repair.