title: Synthes Award for Resident Research on Spinal Cord and Spinal Column Injury: granulocyte macrophage colony stimulating factor (GM-CSF) prevents apoptosis and improves functional outcome in experimental spinal cord contusion injury.
abstract: 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 staurosporine-induced neuronal death model in a Neuro 2A (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 staurosporine for 24 hours. To inhibit GM-CSF, we pretreated N2A cells with antibodies of the GM-CSF receptor for 60 minutes. SCI was made by clip compression. Rats were treated with daily GM-CSF (20 microg/d) 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 phosphate buffered saline (PBS)-treated control. TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeled) 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.
authors.affiliation: Department of Neurosurgery, Inha University College of Medicine, Inchon, Korea.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
authors.forename: Hyune Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Chong Woon
authors.initials: CW
authors.lastname: Park
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Yoon
authors.forename: So Ra
authors.initials: SR
authors.lastname: Park
authors.forename: Dong Keun
authors.initials: DK
authors.lastname: Hyun
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Hyung Chun
authors.initials: HC
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001363:Awards and Prizes; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007396:Internship and Residency; D009493:Neurosurgery / Q000193:education*; D012106:Research; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000601:surgery*; D013124:Spinal Injuries / Q000188:drug therapy* / Q000601:surgery*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor