Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke.

Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke.
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DOI:
10.1016/j.nbd.2009.06.012
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发表时间:
2009-10
影响因子:
6.1
通讯作者:
Chen J
Chen J
中科院分区:
医学1区
文献类型:
--
作者:
Cui X;Chopp M;Zacharek A;Roberts C;Lu M;Savant-Bhonsale S;Chen J

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We investigated the additive therapeutic effect that 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 (1×106) or combination Simvastatin with BMSCs starting at 24 hours 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 were 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.
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