Administration of TSG-6 improves memory after traumatic brain injury in mice

NEUROBIOLOGY OF DISEASE

卷:59

Article

Watanabe, Jun¹  Shetty, Ashok K.¹  Hattiangady, Bharathi¹  Kim, Dong-Ki¹  Foraker, Jessica E.¹  Nishida, Hidetaka¹  Prockop, Darwin J.¹ 

[1] Scott & White Mem Hosp & Clin, Texas A&M Hlth Sci Ctr, Coll Med, Inst Regenerat Med, Temple, TX 76502 USA

关键词: TSG-6;    Mesenchymal stem cells;    Traumatic brain injury;    Blood brain barrier;    Neutrophils;    Matrix metalloproteinase;   

DOI  :  10.1016/j.nbd.2013.06.017

来源: Elsevier

【 摘 要 】

Traumatic brain injury (TBI) causes multiple long-term defects including a loss of working memory that is frequently incapacitating. Administrations of mesenchymal stem/stromal cells (MSCs) previously produced beneficial effects in models of TBI as well as other disease models. In several models, the beneficial effects were explained by the MSCs being activated to express TSG-6, a multifunctional protein that modulates inflammation. In a mouse model of TB!, we found the initial mild phase of the inflammatory response persisted for at least 24 h and was followed by secondary severe response that peaked at 3 days. Intravenous human MSCs or TSG-6 during initial mild phase decreased neutrophil extravasation, expression of matrix metalloproteinase 9 by endothelial cells and neutrophils, and the subsequent blood brain barrier leakage in secondary phase. Administration of TSG-6 also decreased the lesion size at 2 weeks. Importantly, the acute administration of TSG-6 within 24 h of TBI was followed 6 to 10 weeks later by improvements in memory, depressive-like behavior and the number of newly born-neurons. The data suggested that acute administration of TSG-6 may be an effective therapy for decreasing some of the long-term consequences of TBI. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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