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.

Yoon Ha, Hyune Seon Park, Chong Woon Park, Seung Hwan Yoon, S. R. Park, Dong Keun Hyun, Eun Young Kim, Hyung Chun Park

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)341-347
Number of pages7
JournalClinical neurosurgery
Volume52
Publication statusPublished - 2005

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

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