期刊
NEUROBIOLOGY OF DISEASE
卷 36, 期 1, 页码 35-41出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.06.012
关键词
Bone marrow stromal cell; Simvastatin; Arteriogenesis; Angiogenesis; Stroke
资金
- NIA [R01 AG031811]
- NINDS [P01 NS23393, P01 NS042345, R01 NS047682]
- AHA [0750048Z, 09GRNT2300151]
We investigated the additive therapeutic effect of the combination treatment of stroke with sub-therapeutic doses of Simvastatin, a HMG-CoA reductase inhibitor, and bone marrow stromal cells (BMSCs). Rats were administered Simvastatin (0.5 mg/kg), BMSCs (1x10(6)) or combination of Simvastatin and BMSCs starting at 24 h after stroke. Combination treatment significantly improved neurological outcome, enhanced angiogenesis and arteriogenesis, and increased the number of engrafted-BMSCs in the ischemic brain. The number of engrafted-BMSCs and arteriogenesis was significantly correlated with functional outcome. Simvastatin significantly increased stromal cell-derived factor-1 (SDF1) expression in the ischemic brain and chemokine (CXC motif) receptor-4 (CXCR4) in BMSCs, and increased BMSC migration to RBMECs and astrocytes. Combination treatment of stroke upregulates the SDF1/CXCR4 axis and enhances BMSC migration into the ischemic brain, amplifies arteriogenesis and angiogenesis, and improves functional outcome after stroke. (C) 2009 Elsevier Inc. All rights reserved.
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