Granulocyte Colony-Stimulating Factor Improves Motor Function in Rats Developing Compression Myelopathy

Granulocyte Colony-Stimulating Factor Improves Motor Function in Rats Developing Compression Myelopathy
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DOI:
10.1097/brs.0000000000001659
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发表时间:
2016-12
期刊:
影响因子:
3
通讯作者:
T. Yoshizumi;Hidetoshi Murata;Shinji Yamamoto;R. Kurokawa;Phyo Kim;N. Kawahara
T. Yoshizumi;Hidetoshi Murata;Shinji Yamamoto;R. Kurokawa;Phyo Kim;N. Kawahara
中科院分区:
医学2区
文献类型:
--
作者:
T. Yoshizumi;Hidetoshi Murata;Shinji Yamamoto;R. Kurokawa;Phyo Kim;N. Kawahara

文献摘要

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研究设计.基础动物研究。Objective.在大鼠慢性脊髓压迫模型中评估粒细胞集落刺激因子(G-CSF)的作用,以探讨G-CSF作为脊髓型颈椎病药物治疗的潜力。背景数据总结。G-CSF是临床上用于治疗中性粒细胞减少症的造血细胞因子。最近,已经报道了G-CSF在脊髓疾病中的神经保护作用。方法.将聚氨酯薄片植入大鼠C5-C6椎板下,通过吸水逐渐扩张,以建立慢性颈髓压迫模型。该模型再现了颈椎迟发性压迫性脊髓病。在假手术中,床单立即被移除。G-CSF(15 g/kg)或生理盐水(NS)每周5天皮下给药。实验组为假手术组、脊髓压迫组和G-CSF组。为了评估运动功能,测量旋转棒性能和握力。术后26周,对颈脊髓进行组织病理学检查。在预防实验中,手术后立即开始G-CSF或NS给药。在治疗实验中,它们的给药在手术后8周开始。在另一个实验中,在预防实验的三个组中,进行末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-生物素缺口末端标记染色,以评估手术后8周的凋亡性细胞死亡。结果在预防实验中,给予G-CSF在整个26周内保留了运动功能和运动神经元,并在8周时显著减少了凋亡细胞的数量。在治疗实验中,从手术后8周开始给予G-CSF显著地使运动功能暂时恢复到与假手术组相等的水平。结论在大鼠慢性脊髓压迫模型中,G-CSF防止运动功能的下降并保护运动神经元。G-CSF还可改善压迫性脊髓病进展期的运动功能。证据等级:N/A
Study Design. Basic animal research. Objective. The effects of granulocyte colony-stimulating factor (G-CSF) were assessed in a rat chronic spinal cord compression model to explore the potential of G-CSF as a pharmacological treatment for cervical spondylotic myelopathy. Summary of Background Data. G-CSF is a hematopoietic cytokine used clinically to treat neutropenia. Recently, neuroprotective effects of G-CSF have been reported in spinal cord disorders. Methods. To introduce the chronic cervical cord compression, thin polyurethane sheets were implanted under C5-C6 laminae of rats and gradually expanded by absorbing water. This model reproduces delayed compressive myelopathy of the cervical spine. In sham operations, the sheets were immediately removed. G-CSF (15 g/kg) or normal saline (NS) was administered subcutaneously 5 days a week. Experimental groups were sham operation given NS; cord compression given NS; and cord compression given G-CSF. To assess motor functions, rotarod performance, and grip strength were measured. Twenty-six weeks after surgery, cervical spinal cords were examined histopathologically. In the prevention experiment, G-CSF or NS administration was started immediately after surgery. In the treatment experiment, their administration was started 8 weeks after surgery. In another experiment, in three groups in the prevention experiment, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick end labeling staining was performed to assess apoptotic cell death at 8 weeks after surgery. Results. In the prevention experiment, administration of G-CSF preserved the motor functions and motor neurons throughout the 26 weeks, and significantly decreased the number of apoptotic cells at 8 weeks. In the treatment experiment, G-CSF administration from 8 weeks after surgery markedly restored the motor function temporarily to a level equal to the sham group. Conclusion. G-CSF prevents the decline in motor functions and preserves motor neurons in the rat chronic cord compression model. G-CSF also improves motor function in the progressive phase of compression myelopathy. Level of Evidence: N/A