Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.
Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.
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DOI：
10.1371/journal.pone.0050391
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yamazaki M
中科院分区：
文献类型：
--
作者：
Kadota R;Koda M;Kawabe J;Hashimoto M;Nishio Y;Mannoji C;Miyashita T;Furuya T;Okawa A;Takahashi K;Yamazaki M
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，并且我们先前在小鼠脊髓损伤（SCI）的研究中报道了相同的作用。本研究的目的是阐明G-CSF对大鼠SCI的潜在治疗作用。本研究使用成年雌性Sprague-Dawley大鼠。使用Infinite Horizon撞击器（量级：200千达因）引入挫伤性SCI。手术后1小时通过尾静脉注射给予重组人G-CSF（15.0 µg/kg），并在接下来的四天内每天注射一次。溶剂对照大鼠在相同时间点接受等体积的生理盐水。使用挫伤性SCI模型来检查G-CSF的神经保护潜力，我们发现G-CSF在mRNA和蛋白水平上抑制促炎细胞因子（IL-1 β和TNF-α）的表达。用luxol固蓝染色的组织学评估显示，在G-CSF治疗的大鼠中，损伤脊髓中保留的白色物质的面积显著更大。免疫组化结果显示，G-CSF可促进脊髓损伤后少突胶质细胞抗凋亡蛋白Bcl-Xl表达上调，抑制脊髓损伤后少突胶质细胞凋亡。此外，G-CSF的给药促进了更好的后肢功能恢复。G-CSF通过抑制炎性细胞因子和上调抗凋亡蛋白来保护少突胶质细胞免受SCI诱导的细胞死亡。因此，G-CSF减弱了白色物质损失并促进后肢功能恢复。
Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI). The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne). Recombinant human G-CSF (15.0 µg/kg) was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha) in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.
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影响因子：
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