ROLES OF PLASMINOGEN ACTIVATORS UPON BRAIN INJURY

尿激酶型纤溶酶原激活物（uPA）参与组织纤维蛋白溶解，其与愈合过程、发展和肿瘤侵袭有关。纤溶酶原抑制剂-1（派-1）可抑制uPA的蛋白水解活性，并可增强脑损伤后的脑血管。我们研究了uPA缺陷型、uPA受体缺陷型和派-1缺陷型小鼠以及对照小鼠脑刺伤后的脑水肿和血管变化。与对照组小鼠相比，派1缺陷型小鼠的免疫球蛋白外渗在损伤后3天显著更大，uPA缺陷型小鼠不太明显，而uPA受体缺陷型小鼠与对照组相似。血管性血友病因子阳性血管结构的数量增加8天后，在派-1缺陷型小鼠病变。此外，在所有派-1缺陷小鼠和20%的对照小鼠中观察到病变放置后8天的不规则和增殖的IV型胶原阳性微血管。这些发现表明血管生成增加。我们的研究清楚地表明，由于微血管细胞外基质蛋白的分解，uPA有助于继发性脑损伤的发展，并且uPA在急性期发挥作用而不与其受体结合。派-1抑制创伤性脑水肿。另一方面，纤溶酶原激活剂促进脑损伤后愈合所必需的血管生成。

Urokinase type plasminogen activator (uPA) involves tissue fibrinolysis that is related to the healing process, development, and tumor invasion. Plasminogen inhibitor-1 (PAI-1) inhibits the protelytic activity of uPA and may enhance the brain vasculature after brain injury. We studied brain edema and changes in the vasculature after a brain stab wound in uPA-deficient, uPA receptor-deficient, and PAI-1-deficient mice, and control mice. Compared to control mice, the extravasation of immunoglobulin was significantly greater in PAI 1 deficient mice at 3 days after the lesion was placed, less pronounced in uPA-deficient mice and similar to the controls in uPA receptor-deficient mice. Von Willebrand factor-positive vascular structures increased in number 8 days after lesioning in PAI-1 deficient mice. Furthermore, irregular and proliferative collagen Type IV-positive microvasculatures were observed in all PAI-1-deficient mice and in 20% of control mice 8 days after lesion placement. Those findings are indicative of increased angiogenesis. Our study clearly shows that uPA contributes to the development of secondary brain damage due to a breakdown of microvascular extracellular matrix protein, and that uPA plays a role without binding to its receptor in the acute stage. PAI-1 inhibits traumatic brain edema. On the other hand, plasminogen activator facilitates angiogenesis necessary for healing after brain injury.