State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao,
Metab Brain Dis. 2013 Dec;28(4):655-66. doi: 10.1007/s11011-013-9425-z. Epub 2013 Aug 17.
Combining bone marrow stromal cells (BMSCs) with pharmacological therapy is an attractive approach for neurological function recovery of stroke. Our previous reports demonstrated that Sodium Ferulate (SF) combined with BMSCs administration could facilitate BMSCs migration into the ischemic brain by up-regulation of stromal cell-derived factor-1 alpha (SDF-1α)/chemokine (CXC motif) receptor-4 axis after stroke. To further investigate whether combination treatment could enhance neurogenesis through exogenous and endogenous therapeutic effects, we established rat permanent middle cerebral artery occlusion (pMCAo) model and measured ischemic infarct size by magnetic resonance imaging (MRI) scanning in the present study. The results showed that combination treatment could dramatically reduce ischemic infarction size which may be attributed to the effects on decreasing brain edema and enhancing cerebral tissue perfusion at 3 days after stroke. Immunofluorescence staining results indicated that combination treatment could not only promote expression of Glucose transporter 1(Glut1) and Neuron-specific class III beta-tubulin (Tuj1) in the periinfarct area, but also improve BMSCs expression of Glut1, GFAP and Tuj1. Moreover, it showed combination treatment could enhance the endogenous expression of Tuj-1 in ischemic boundary zone. These results perhaps associated with combination treatment up-regulating bone morphogenetic proteins (BMP)2/4 expressions and down-regulating Notch-1, Hes1 and Hes5 expressions as detected by Western Blot analysis. Our study firstly demonstrated in vivo that combination treatment could facilitate exogenous BMSCs differentiation into neural-and astrocytic-like cells, as well as enhance repair capacity of brain parenchymal cells by promoting glucose metabolism and endogenous neurogenesis after stroke. These results illustrate that administration of SF and BMSCs is a potential pathway of cell-based pharmacological treatment towards ischemic stroke.
将骨髓基质细胞（BMSCs）与药物治疗相结合是一种有吸引力的方法，可用于恢复中风后的神经功能。我们之前的报告表明，阿魏酸钠（SF）与 BMSCs 联合给药可以通过上调基质细胞衍生因子-1 ɑ（SDF-1α）/趋化因子（CXC 基序）受体-4 轴来促进 BMSCs 迁移到缺血性大脑，从而促进 BMSCs 迁移到缺血性大脑中风后。为了进一步研究联合治疗是否可以通过外源性和内源性治疗效果来增强神经发生，我们在本研究中建立了大鼠永久性大脑中动脉闭塞（pMCAo）模型，并通过磁共振成像（MRI）扫描测量缺血性梗死面积。结果表明，联合治疗可以显著减少缺血性梗死面积，这可能归因于在中风后 3 天减少脑水肿和增强脑组织灌注的作用。免疫荧光染色结果表明，联合治疗不仅可以促进梗塞周围区域葡萄糖转运蛋白 1（Glut1）和神经元特异性 III 类β-微管蛋白（Tuj1）的表达，还可以改善 BMSCs 中 Glut1、GFAP 和 Tuj1 的表达。此外，它表明联合治疗可以增强缺血边界区的内源性 Tuj-1 表达。这些结果可能与联合治疗上调骨形态发生蛋白（BMP）2/4 的表达以及下调 Notch-1、Hes1 和 Hes5 的表达有关，这通过 Western Blot 分析检测到。我们的研究首次在体内证明，联合治疗可以促进外源性 BMSCs 分化为神经和星形细胞样细胞，并通过促进葡萄糖代谢和内源性神经发生来增强脑实质细胞的修复能力中风后。这些结果表明，SF 和 BMSCs 的给药是细胞药物治疗缺血性中风的潜在途径。
