Department of Neurosurgery, Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13287-92. doi: 10.1073/pnas.1107368108. Epub 2011 Jul 26.
Tissue plasminogen activator is the only treatment option for stroke victims; however, it has to be administered within 4.5 h after symptom onset, making its use very limited. This report describes a unique target for effective treatment of stroke, even 12 h after onset, by the administration of αB-crystallin (Cryab), an endogenous immunomodulatory neuroprotectant. In Cryab(-/-) mice, there was increased lesion size and diminished neurologic function after stroke compared with wild-type mice. Increased plasma Cryab was detected after experimental stroke in mice and after stroke in human patients. Administration of Cryab even 12 h after experimental stroke reduced both stroke volume and inflammatory cytokines associated with stroke pathology. Cryab is an endogenous anti-inflammatory and neuroprotectant molecule produced after stroke, whose beneficial properties can be augmented when administered therapeutically after stroke.
组织型纤溶酶原激活物是脑卒中患者唯一的治疗选择;但是,它必须在症状发作后 4.5 小时内使用,因此其应用非常有限。本报告介绍了一种独特的靶点,通过给予αB-晶体蛋白(Cryab),一种内源性免疫调节神经保护剂,即使在发病后 12 小时也可有效治疗脑卒中。与野生型小鼠相比,Cryab(-/-)小鼠在脑卒中后其损伤体积增大,神经功能下降。在实验性脑卒中后的小鼠和人类患者的脑卒中后均检测到血浆 Cryab 增加。即使在实验性脑卒中后 12 小时给予 Cryab,也可减少脑卒中体积和与脑卒中病理相关的炎症细胞因子。Cryab 是脑卒中后产生的一种内源性抗炎和神经保护分子,当在脑卒中后进行治疗性给予时,其有益特性可增强。