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Granulocyte Colony-Stimulating Factor Improves Motor Function in Rats Developing Compression Myelopathy
Tetsuya Yoshizumi1, Hidetoshi Murata1, Shinji Yamamoto2
1Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan.
Insights
Granulocyte colony-stimulating factor (G-CSF) prevents motor decline and preserves motor neurons in a rat model of chronic spinal cord compression. G-CSF also improves motor function during the progressive phase of this condition.
Area of Science:
- Neuroscience
- Pharmacology
- Spinal Cord Injury Research
Background:
- Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine with recently identified neuroprotective properties in spinal cord disorders.
- Cervical spondylotic myelopathy is a condition characterized by chronic spinal cord compression.
Purpose of the Study:
- To evaluate the efficacy of G-CSF as a potential pharmacological treatment for cervical spondylotic myelopathy.
- To assess the neuroprotective and functional recovery effects of G-CSF in a rat model of chronic spinal cord compression.
Main Methods:
- A rat model of chronic cervical spinal cord compression was established by implanting and gradually expanding polyurethane sheets.
- Granulocyte colony-stimulating factor (G-CSF) or normal saline was administered subcutaneously in prevention and treatment experimental groups.
- Motor function was assessed using rotarod performance and grip strength, and spinal cords were examined histopathologically, including apoptotic cell death assessment.
Main Results:
- G-CSF administration in the prevention experiment preserved motor function and motor neurons over 26 weeks and reduced apoptotic cell death at 8 weeks.
- In the treatment experiment, G-CSF administration initiated 8 weeks post-surgery significantly restored motor function temporarily.
- Histopathological examination confirmed the preservation of motor neurons by G-CSF.
Conclusions:
- G-CSF demonstrates potential as a therapeutic agent for cervical spondylotic myelopathy by preventing motor function decline and preserving motor neurons.
- G-CSF can improve motor function even in the progressive stages of compression myelopathy.
Study Design:
Basic animal research.
Objective:
The effects of granulocyte colony-stimulating factor (G-CSF) were assessed in a rat chronic spinal cord compression model to explore the potential of G-CSF as a pharmacological treatment for cervical spondylotic myelopathy.
Summary Of Background Data:
G-CSF is a hematopoietic cytokine used clinically to treat neutropenia. Recently, neuroprotective effects of G-CSF have been reported in spinal cord disorders.
Methods:
To introduce the chronic cervical cord compression, thin polyurethane sheets were implanted under C5-C6 laminae of rats and gradually expanded by absorbing water. This model reproduces delayed compressive myelopathy of the cervical spine. In sham operations, the sheets were immediately removed. G-CSF (15 μg/kg) or normal saline (NS) was administered subcutaneously 5 days a week. Experimental groups were sham operation given NS; cord compression given NS; and cord compression given G-CSF. To assess motor functions, rotarod performance, and grip strength were measured. Twenty-six weeks after surgery, cervical spinal cords were examined histopathologically. In the prevention experiment, G-CSF or NS administration was started immediately after surgery. In the treatment experiment, their administration was started 8 weeks after surgery. In another experiment, in three groups in the prevention experiment, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining was performed to assess apoptotic cell death at 8 weeks after surgery.
Results:
In the prevention experiment, administration of G-CSF preserved the motor functions and motor neurons throughout the 26 weeks, and significantly decreased the number of apoptotic cells at 8 weeks. In the treatment experiment, G-CSF administration from 8 weeks after surgery markedly restored the motor function temporarily to a level equal to the sham group.
Conclusion:
G-CSF prevents the decline in motor functions and preserves motor neurons in the rat chronic cord compression model. G-CSF also improves motor function in the progressive phase of compression myelopathy.
Level Of Evidence:
N/A.
