Department of Neurology, University of Münster Münster, Germany.
Fraunhofer Institute for Cell Therapy and Immunology Leipzig, Germany ; Translational Center for Regenerative Medicine, University of Leipzig Leipzig, Germany.
Front Cell Neurosci. 2014 Dec 4;8:411. doi: 10.3389/fncel.2014.00411. eCollection 2014.
Granulocyte-colony stimulating factor (G-CSF) and bone marrow derived mononuclear cells (BM-MNCs) have both been shown to improve functional outcome following experimental stroke. These effects are associated with increased angiogenesis and neurogenesis. In the present study, we aimed to determine synergistic effects of G-CSF and BM-NMC treatment on long-term structural and functional recovery after photothrombotic stroke. To model the etiology of stroke more closely, we used spontaneously hypertensive (SH) rats in our experiment. Bone marrow derived mononuclear cells transplantation was initiated 1 h after the onset of photothrombotic stroke. Repeated G-CSF treatment commenced immediately after BM-MNC treatment followed by daily injections for five consecutive days. The primary endpoint was functional outcome after ischemia. Secondary endpoints included analysis of neurogenesis and angiogenesis as well as determination of infarct size. Granulocyte-colony stimulating factor treated rats, either in combination with BM-MNC or alone showed improved somatosensory but not gross motor function following ischemia. No beneficial effect of BM-MNC monotherapy was found. Infarct volumes were comparable in all groups. In contrast to previous studies, which used healthy animals, post-stroke neurogenesis and angiogenesis were not enhanced by G-CSF. In conclusion, the combination of G-CSF and BM-MNC was not more effective than G-CSF alone. The reduced efficacy of G-CSF treatment and the absence of any beneficial effect of BM-MNC transplantation might be attributed to hypertension-related morbidity.
粒细胞集落刺激因子(G-CSF)和骨髓来源的单核细胞(BM-MNCs)均已被证明可改善实验性中风后的功能预后。这些作用与血管生成和神经发生的增加有关。在本研究中,我们旨在确定 G-CSF 和 BM-NMC 联合治疗对光血栓性中风后长期结构和功能恢复的协同作用。为了更紧密地模拟中风的病因,我们在实验中使用了自发性高血压(SH)大鼠。骨髓来源的单核细胞移植在光血栓性中风发作后 1 小时开始。在 BM-MNC 治疗后立即开始重复 G-CSF 治疗,随后连续 5 天每天注射。主要终点是缺血后的功能预后。次要终点包括神经发生和血管生成的分析以及梗塞面积的测定。在缺血后,接受 G-CSF 治疗的大鼠,无论是单独治疗还是与 BM-MNC 联合治疗,体感功能均有所改善,但运动功能无明显改善。BM-MNC 单独治疗未发现有益作用。与以前使用健康动物的研究不同,中风后神经发生和血管生成未被 G-CSF 增强。总之,G-CSF 与 BM-MNC 的联合应用并不比 G-CSF 单独应用更有效。G-CSF 治疗效果降低以及 BM-MNC 移植无任何有益作用可能归因于与高血压相关的发病率。