Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice
Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice
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DOI：
10.1097/nen.0b013e3181257176
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发表时间：
2007-08-01
影响因子：
3.2
通讯作者：
Yamazaki, Masashi
中科院分区：
文献类型：
--
作者：
Nishio, Yutaka;Koda, Masao;Yamazaki, Masashi
粒细胞集落刺激因子（G-CSF）是一种刺激粒细胞谱系细胞分化、增殖和存活的蛋白质。最近，在脑梗死模型中报道了G-CSF的神经保护作用。本研究的目的是阐明G-CSF对小鼠脊髓损伤（SCI）的潜在治疗作用。我们发现G-CSF对谷氨酸诱导的小脑颗粒神经元细胞死亡具有神经保护作用。此外，我们使用了小鼠模型的压缩性脊髓损伤，以检查在体内的神经保护潜力的G-CSF。用甲酚紫染色的组织学评估显示，在G-CSF处理的小鼠中，受损脊髓中存活的神经元的数量显著增加。神经细胞凋亡的免疫组化显示，G-CSF抑制脊髓损伤后神经细胞凋亡。此外，G-CSF的管理促进后肢功能的恢复。对G-CSF受体下游信号通路的研究表明，G-CSF可能通过抑制SCI后神经元凋亡促进功能恢复。G-CSF目前在临床上用于造血刺激，其正在进行的脑梗死临床试验使其成为一种有吸引力的分子，可以迅速用于急性SCI患者的试验。
Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immuno-histochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.