Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury.

Yoon Ha, Young Soo Kim, Jin Mo Cho, Seung Hwan Yoon, S. R. Park, Do Heum Yoon, Eun Young Kim, Hyung Chun Park

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

OBJECT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hemopoietic cytokine that stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. Its effects in the central nervous system, however, are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurological function in a spinal cord injury (SCI) model. METHODS: To study the effect of GM-CSF on apoptotic neuronal death, the authors used a staurosporine-induced neuronal death model in an N2A cell line (in vitro) and in a rat SCI model (in vivo). The N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, N2A cells were pretreated with antibodies against the GM-CSF receptor for 60 minutes. Clip compression was,used to induce SCI. Animals were treated with daily doses of GM-CSF (20 microg/day) for 5 days. The number of apoptotic cells in the spinal cord and neurological improvements were assessed. Pretreatment with GM-CSF was found to protect N2A cells significantly from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurological function improved significantly in the GM-CSF-treated group compared with controls treated with phosphate-buffered saline. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. CONCLUSIONS: Treatment of SCI with GM-CSF showed 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)55-61
Number of pages7
JournalJournal of neurosurgery. Spine
Volume2
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

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Granulocyte-Macrophage Colony-Stimulating Factor
Spinal Cord Injuries
Apoptosis
Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Staurosporine
Spinal Cord
DNA Nucleotidylexotransferase
Therapeutic Uses
Neutralizing Antibodies
Surgical Instruments
Leukocytes
Cell Death
Stem Cells
Central Nervous System
Cell Count
Bone Marrow
Phosphates
Cell Proliferation
Staining and Labeling
Cytokines

All Science Journal Classification (ASJC) codes

  • Surgery
  • Neurology
  • Clinical Neurology

Cite this

Ha, Yoon ; Kim, Young Soo ; Cho, Jin Mo ; Yoon, Seung Hwan ; Park, S. R. ; Yoon, Do Heum ; Kim, Eun Young ; Park, Hyung Chun. / Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury. In: Journal of neurosurgery. Spine. 2005 ; Vol. 2, No. 1. pp. 55-61.
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abstract = "OBJECT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hemopoietic cytokine that stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. Its effects in the central nervous system, however, are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurological function in a spinal cord injury (SCI) model. METHODS: To study the effect of GM-CSF on apoptotic neuronal death, the authors used a staurosporine-induced neuronal death model in an N2A cell line (in vitro) and in a rat SCI model (in vivo). The N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, N2A cells were pretreated with antibodies against the GM-CSF receptor for 60 minutes. Clip compression was,used to induce SCI. Animals were treated with daily doses of GM-CSF (20 microg/day) for 5 days. The number of apoptotic cells in the spinal cord and neurological improvements were assessed. Pretreatment with GM-CSF was found to protect N2A cells significantly from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurological function improved significantly in the GM-CSF-treated group compared with controls treated with phosphate-buffered saline. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. CONCLUSIONS: Treatment of SCI with GM-CSF showed beneficial effects. Neuronal protection against apoptosis is viewed as a likely mechanism underlying the therapeutic effect of GM-CSF in SCI.",
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Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury. / Ha, Yoon; Kim, Young Soo; Cho, Jin Mo; Yoon, Seung Hwan; Park, S. R.; Yoon, Do Heum; Kim, Eun Young; Park, Hyung Chun.

In: Journal of neurosurgery. Spine, Vol. 2, No. 1, 01.01.2005, p. 55-61.

Research output: Contribution to journalArticle

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T1 - Role of granulocyte-macrophage colony-stimulating factor in preventing apoptosis and improving functional outcome in experimental spinal cord contusion injury.

AU - Ha, Yoon

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AU - Yoon, Do Heum

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AU - Park, Hyung Chun

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N2 - OBJECT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hemopoietic cytokine that stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. Its effects in the central nervous system, however, are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurological function in a spinal cord injury (SCI) model. METHODS: To study the effect of GM-CSF on apoptotic neuronal death, the authors used a staurosporine-induced neuronal death model in an N2A cell line (in vitro) and in a rat SCI model (in vivo). The N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, N2A cells were pretreated with antibodies against the GM-CSF receptor for 60 minutes. Clip compression was,used to induce SCI. Animals were treated with daily doses of GM-CSF (20 microg/day) for 5 days. The number of apoptotic cells in the spinal cord and neurological improvements were assessed. Pretreatment with GM-CSF was found to protect N2A cells significantly from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurological function improved significantly in the GM-CSF-treated group compared with controls treated with phosphate-buffered saline. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. CONCLUSIONS: Treatment of SCI with GM-CSF showed beneficial effects. Neuronal protection against apoptosis is viewed as a likely mechanism underlying the therapeutic effect of GM-CSF in SCI.

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