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.
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.
Ha
Yoon
Y
Department of Neurosurgery, Inha University College of Medicine, Inchon, Korea.
Park
Hyune Seon
HS
Park
Chong Woon
CW
Yoon
Seung Hwan
SH
Park
So Ra
SR
Hyun
Dong Keun
DK
Kim
Eun Young
EY
Park
Hyung Chun
HC
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*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor