Nishio Yutaka, Koda Masao, Kamada Takahito, Someya Yukio, Kadota Ryo, Mannoji Chikato, Miyashita Tomohiro, Okada Seiji, Okawa Akihiko, Moriya Hideshige, Yamazaki Masashi
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Neuropathol Exp Neurol. 2007 Aug;66(8):724-31. doi: 10.1097/nen.0b013e3181257176.
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. Immunohistochemistry 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.
粒细胞集落刺激因子（G-CSF）是一种刺激粒细胞系细胞分化、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在体外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，我们使用压迫性SCI小鼠模型来研究G-CSF在体内的神经保护潜力。用甲酚紫染色进行组织学评估显示，G-CSF治疗的小鼠损伤脊髓中存活神经元的数量显著增加。神经元凋亡的免疫组织化学显示，G-CSF抑制了SCI后的神经元凋亡。此外，G-CSF的给药促进了后肢功能恢复。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后的神经元凋亡来促进功能恢复。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。
