Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice.
Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immunohistochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.
Nishio
Yutaka
Y
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Koda
Masao
M
Kamada
Takahito
T
Someya
Yukio
Y
Kadota
Ryo
R
Mannoji
Chikato
C
Miyashita
Tomohiro
T
Okada
Seiji
S
Okawa
Akihiko
A
Moriya
Hideshige
H
Yamazaki
Masashi
M
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013997:Time Factors
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase