Granulocyte Colony-Stimulating Factor (G-CSF) Protects Oligpdendrocyte and Promotes Hindlimb Functional Recovery after Spinal Cord Injury in Rats

Abstract

BackgroundGranulocyte 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.MethodsAdult 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.ResultsUsing 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.ConclusionsG-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.

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

“…12 In this study, G-CSF induced rapid recovery of motor functions in developing compression myelopathy ( Figures 6, 7), and inhibited apoptotic cell death in the anterior horn in chronic cervical cord compression (Figures 5a, b). These findings suggest that G-CSF can act directly on neurons and oligodendrocytes in the spinal cord.…”

“…The pleiotropic mechanisms of the beneficial effects of G-CSF in acute spinal cord injury include promotion of migration of bone marrow-derived cells, 19 induction of proliferation of oligodendroglial precursors, 20 inhibition of apoptotic cell death, [12][13][14][15] angiogenesis, 21 and suppression of inflammatory cytokines. 12 In this study, G-CSF induced rapid recovery of motor functions in developing compression myelopathy ( Figures 6, 7), and inhibited apoptotic cell death in the anterior horn in chronic cervical cord compression (Figures 5a, b).…”

“…In the prevention experiment, 36 rats were allocated to Group A (n = 12), Group B (n = 12), and Group C (n = 12), and the motor functions and sparing of motor neurons in the anterior horn were assessed. Furthermore, another 18 rats were equally allocated to these three groups, sacrificed at 8 weeks, and then apoptotic cells were detected and counted with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL).…”

Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats

“…Rats in the vehicle group received an equivalent volume of normal saline at the same time points. We followed the drug-administration regimen described in our previous report of our rat model of SCI [10]. On the day following the final administration of G-CSF, peripheral blood samples were collected for leukocyte counts.…”

“…G-CSF was found to protect neurons from ischemia-induced cell death and to promote neurogenesis in a rat model of brain ischemia [7,8]. Recently we reported that G-CSF protects neurons and oligodendrocytes from apoptosis in mouse and rat SCI models [9,10]. Moreover, it was reported that G-CSF attenuates peripheral NeP [11,12].…”