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


BACKGROUND
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.


CONCLUSIONS
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.


METHODS
N/A.
Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan.
Tetsuya
T
Yoshizumi
Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan.
Hidetoshi
H
Murata
Department of Neurologic Surgery, Dokkyo Medical University Hospital, Tochighi, Japan.
Shinji
S
Yamamoto
Department of Neurologic Surgery, Dokkyo Medical University Hospital, Tochighi, Japan.
Ryu
R
Kurokawa
Department of Neurologic Surgery, Dokkyo Medical University Hospital, Tochighi, Japan.
Phyo
P
Kim
Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan.
Nobutaka
N
Kawahara
D000818:Animals; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000503:physiopathology
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor