Abstract
Acidic fibroblast growth factor (aFGF; also known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. However, the pathological changes that occur with spinal cord injury (SCI) and the attribution to aFGF of a neuroprotective effect during SCI are still elusive. In this study, we demonstrated that rat SCI, when treated with aFGF, showed significant functional recovery as indicated by the Basso, Beattie, and Bresnahan locomotor rating scale and the combined behavior score (p < 0.01-0.001). Furthermore proteomics and bioinformatics approaches were adapted to investigate changes in the global protein profile of the damaged spinal cord tissue when experimental rats were treated either with or without aFGF at 24 h after injury. We found that 51 protein spots, resolvable by two-dimensional PAGE, had significant differential expression. Using hierarchical clustering analysis, these proteins were categorized into five major expression patterns. Noticeably proteins involved in the process of secondary injury, such as astrocyte activation (glial fibrillary acidic protein), inflammation (S100B), and scar formation (keratan sulfate proteoglycan lumican), which lead to the blocking of injured spinal cord regeneration, were down-regulated in the contusive spinal cord after treatment with aFGF. We propose that aFGF might initiate a series of biological processes to prevent or attenuate secondary injury and that this, in turn, leads to an improvement in functional recovery. Moreover the quantitative expression level of these proteins was verified by quantitative real time PCR. Furthermore we identified various potential neuroprotective protein factors that are induced by aFGF and may be involved in the spinal cord repair processes of SCI rats. Thus, our results could have a remarkable impact on clinical developments in the area of spinal cord injury therapy.
Highlights
Acidic fibroblast growth factor is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord
Quantitative high resolution two-dimensional (2D) PAGE followed by highly accurate LC-MS/MS analysis and a bioinformatics approach was used to functionally cluster and annotate the data collected by proteomics study, and we found that expression of glial fibrillary acidic proteins (GFAPs), S100B, keratan sulfate proteoglycan lumican (KSPG) were up-regulated after spinal cord injury (SCI) and down-regulated following Acidic fibroblast growth factor (aFGF) treatment
We demonstrated using animal behavior tests that a single bolus injection of aFGF is able to induce effective functional recovery after contusive spinal cord injury of rats in vivo (Fig. 1)
Summary
Acidic fibroblast growth factor (aFGF; known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. Spinal cord injury often causes permanent neurological deficits mostly because the injured neurons lack regenerative ability, and the series of destructive processes that follow SCI results in a second wave of cell death and spreading tissue loss [10]. Limited amounts of neurotrophic factors are produced in the adult CNS after injury, and delivery of these neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration [11,12,13]. These results probably indicate that there is a deficiency in these neurotrophic factors that produces the absence of spontaneous regeneration in the spinal cord
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