Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury
Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury
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DOI：
10.3171/spi.2005.2.1.0055
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Park, HC
中科院分区：
文献类型：
--
作者：
Ha, Y;Kim, YS;Park, HC
Object.粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种有效的造血细胞因子，可刺激骨髓中的干细胞增殖并抑制白细胞中的凋亡细胞死亡。然而，它对中枢神经系统的影响仍不清楚。本研究旨在确定GM-CSF是否可以在脊髓损伤（SCI）模型中拯救神经细胞免于凋亡并改善神经功能。方法.为了研究GM-CSF对凋亡性神经元死亡的影响，作者在N2 A细胞系（体外）和大鼠SCI模型（体内）中使用了星形孢菌素诱导的神经元死亡模型。将N2 A细胞与GM-CSF预孵育60分钟，然后暴露于星形孢菌素24小时。为了抑制GM-CSF，用针对GM-CSF受体的抗体预处理N2 A细胞60分钟。使用成形夹压迫诱导SCI。用每日剂量的GM-CSF（20 μ g/天）处理动物5天。评估脊髓中凋亡细胞的数量和神经功能的改善。GM-CSF预处理可明显抑制N2 A细胞的凋亡，而GM-CSF受体的中和抗体可抑制GM-CSF对N2 A细胞凋亡的挽救作用。在大鼠SCI模型中，与磷酸盐缓冲盐水治疗的对照组相比，GM-CSF治疗组的神经功能显著改善。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记染色显示，GM-CSF给药减少了损伤脊髓的细胞凋亡。结论.用GM-CSF治疗SCI显示出有益的效果。神经元抗凋亡保护被认为是脊髓损伤中GM-CSF治疗作用的潜在机制。
Object. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hemopoietic cytokine that stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. Its effects in the central nervous system, however, are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurological function in a spinal cord injury (SCI) model. Methods. To study the effect of GM-CSF on apoptotic neuronal death, the authors used a staurosporine-induced neuronal death model in an N2A cell line (in vitro) and in a rat SCI model (in vivo). The N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, N2A cells were pretreated with antibodies against the GM-CSF receptor for 60 minutes. Clip compression was used to induce SCI. Animals were treated with daily doses of GM-CSF (20 mug/day) for 5 days. The number of apoptotic cells in the spinal cord and neurological improvements were assessed. Pretreatment with GM-CSF was found to protect N2A cells significantly from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurological function improved significantly in the GM-CSF-treated group compared with controls treated with phosphatebuffered saline. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. Conclusions. Treatment of SCI with GM-CSF showed beneficial effects. Neuronal protection against apoptosis is viewed as a likely mechanism underlying the therapeutic effect of GM-CSF in SCI.