Stromal cell-derived factor-1α promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats
Stromal cell-derived factor-1α promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats
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DOI：
10.1124/jpet.107.127746
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发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Li, Hung
中科院分区：
文献类型：
--
作者：
Shyu, Woei-Cherng;Lin, Shinn-Zong;Li, Hung
基质细胞衍生因子（SDF）-1 α参与造血干细胞从骨髓到外周血的运输，并且其表达在缺血性脑的半暗带中增加。在这项研究中，SDF-1 α被发现发挥神经保护作用，拯救原代皮质培养H2 O2神经毒性，并调节神经营养因子的表达。接受脑内注射SDF-1 α的大鼠由于抗凋亡蛋白的上调而表现出较少的脑梗死，并且它们的运动表现有所改善。SDF-1 α注射增强了骨髓（BM）衍生细胞对受损脑的靶向作用，如患有脑缺血的绿色荧光蛋白嵌合体小鼠所示。此外，SDF-1 α治疗大鼠的缺血皮质中血管密度增加，增强了功能性局部脑血流量。总之，脑内给予SDF-1 α可产生针对神经毒性损伤的神经保护作用，并诱导BM衍生细胞靶向缺血性脑，从而减少脑梗死体积并改善神经可塑性。
Stromal cell- derived factor (SDF)-1 alpha is involved in the trafficking of hematopoietic stem cells from bone marrow to peripheral blood, and its expression is increased in the penumbra of the ischemic brain. In this study, SDF-1 alpha was found to exert neuroprotective effects that rescued primary cortical cultures from H2O2 neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1 alpha showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1 alpha injection enhanced the targeting of bone marrow (BM)-derived cells to the injured brain, as demonstrated in green fluorescent protein-chimeric mice with cerebral ischemia. In addition, increased vascular density in the ischemic cortex of SDF-1 alpha-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1 alpha resulted in neuroprotection against neurotoxic insult, and it induced increased BM-derived cell targeting to the ischemic brain, thereby reducing the volume of cerebral infarction and improving neural plasticity.