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.
Highlights
Acute spinal cord injury (SCI) is divided into two pathological phases termed primary and secondary injury [1]
Granulocyte colony-stimulating factor (G-CSF) Receptor (G-CSFR) Expression To assess the expression of G-CSFR, we performed immunofluorescence analysis on histological sections of spinal cords
G-CSFR was expressed on glial fibrillary acidic protein (GFAP) -positive astrocytes and myelin oligodendrocytespecific protein (MOSP) -positive oligodendrocytes (Fig. 1)
Summary
Acute spinal cord injury (SCI) is divided into two pathological phases termed primary and secondary injury [1]. The primary injury consists of focal tissue destruction caused by direct mechanical trauma. This physical insult initiates the second phase of injury which is a pathophysiological reaction of spinal cord. High-dose methylprednisolone (MP) in acute SCI is an accepted treatment for attenuation of secondary injury [6]. It has become controversial in recent years due to the risk of serious adverse effects and its modest neurological benefits [7]. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats
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