Granulocyte Colony-Stimulating Factor Improves Motor Function in Rats Developing Compression Myelopathy

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 2016-12, Vol.41 (23), p.E1380-E1387
• Main Authors: Yoshizumi, Tetsuya, Murata, Hidetoshi, Yamamoto, Shinji, Kurokawa, Ryu, Kim, Phyo, Kawahara, Nobutaka
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; Motor Neurons - drug effects; Neuroprotective Agents - pharmacology; Rats; Recovery of Function - drug effects; Recovery of Function - physiology; Spinal Cord Compression - drug therapy; Spinal Cord Compression - physiopathology
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/BRS.0000000000001659

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 EvidenceN/A