Systemic augmentation of αB-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation

被引:115
作者
Arac, Ahmet [1 ,2 ,3 ]
Brownell, Sara E. [1 ,4 ,5 ]
Rothbard, Jonathan B. [6 ]
Chen, Charlene [1 ,3 ,5 ]
Ko, Rose M. [6 ]
Pereira, Marta P. [1 ,2 ,3 ]
Albers, Gregory W. [1 ,3 ,5 ]
Steinman, Lawrence [1 ,5 ]
Steinberg, Gary K. [1 ,2 ,3 ]
机构
[1] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Stanford Stroke Ctr, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Biol, Stanford, CA 94305 USA
[5] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[6] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
immune system; ischemic stroke; TISSUE-PLASMINOGEN ACTIVATOR; FOCAL-CEREBRAL-ISCHEMIA; EXPERIMENTAL STROKE; BRAIN-INJURY; T-CELLS; PROTEIN; INHIBITION; APOPTOSIS; CASPASE-3; DISEASE;
D O I
10.1073/pnas.1107368108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 alpha B-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.
引用
收藏
页码:13287 / 13292
页数:6
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