Yepes Manuel
Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Department of Neurology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
J Transl Neurosci. 2018;3(2). Epub 2018 Mar 20.
Synaptic dysfunction underlies the development of neurological impairment following an acute ischemic stroke. Unfortunately, to this date there is no therapeutic approach to protect and repair the synapse that has suffered an ischemic injury. However, recent research with models of hypoxia, models of cerebral ischemia and different neuroradiological techniques has revealed that during the recovery phase from a hypoxic injury neurons release the serine proteinase urokinase-type plasminogen activator (uPA) and astrocytes recruit its receptor (uPAR) to their plasma membrane; and that binding of neuronal uPA to astrocytic uPAR promotes the recovery of the "tripartite synapse" that has suffered an acute ischemic injury. The translational relevance of these findings is underscored by the fact that intravenous treatment with recombinant uPA promotes synaptic recovery and functional improvement following an acute ischemic stroke.
突触功能障碍是急性缺血性中风后神经功能缺损发展的基础。不幸的是，迄今为止，尚无治疗方法可保护和修复遭受缺血性损伤的突触。然而，最近利用缺氧模型、脑缺血模型和不同神经放射学技术进行的研究表明，在从缺氧损伤恢复的阶段，神经元会释放丝氨酸蛋白酶尿激酶型纤溶酶原激活剂（uPA），星形胶质细胞会将其受体（uPAR）募集到其质膜上；并且神经元uPA与星形胶质细胞uPAR的结合促进了遭受急性缺血性损伤的“三联突触”的恢复。重组uPA静脉治疗可促进急性缺血性中风后的突触恢复和功能改善，这一事实凸显了这些发现的转化意义。
