Granulocyte Macrophage Colony stimulating factor (GM-CSF) prevents apoptosis and improves functional outcome in experimental spinal cord contusion injury

초록

Objective: Granulocyte Macrophage colony stimulating factor (GM-CSF) is a potent hematopoietic cytokine, which stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. However, the effects of GM-CSF in the central nervous system are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurologic function in a spinal cord injury (SCI) model. Methods: To study the effect of GM-CSF on apoptotic neuronal death, we used a staurosporin induced neuronal death model in a N2A cell line (in vitro) and in a rat SCI model (in vivo). N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporin for 24hrs. To inhibit GM-CSF, we pretreated N2A cells with antibodies of the GM-CSF receptor for 60min. SCI was made by clip compression. Animals were treated with daily GM-CSF (20ug/day) for 5 days. The number of apoptotic cells in the spinal cord and neurologic improvements were checked. Results: GM-CSF pretreatment was found to significantly protect N2A cells from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurologic functions improved significantly in the GM-CSF administered group versus the PBS treated control. TUNEL staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. Conclusions: Treatment of SCI with GM-CSF showed some beneficial effects. Neuronal protection against apoptosis is viewed as a likely mechanism underlying the therapeutic effect of GM-CSF in SCI. Key words: Spinal cord injury (SCI), Granulocyte macrophage colony stimulating factor (GM-CSF), apoptosis