Delayed granulocyte colony-stimulating factor treatment promotes functional recovery in rats with severe contusive spinal cord injury.
METHODS
We used a severe contusive spinal cord injury (SCI) model and electrophysiologic, motor functional, immunohistochemical, and electron microscopic examinations to analyze the neuroprotective effects of delayed granulocyte colony-stimulating factor (G-CSF) treatment.


OBJECTIVE
To determine the neuroprotective effects of delayed G-CSF treatment using multimodality evaluations after severe contusive SCI in rats.


BACKGROUND
Despite some reports that G-CSF treatment in the acute stage of different central nervous system injury models was neuroprotective, it has not been determined whether delayed G-CSF treatment can promote neural recovery in severe contusive SCI.


METHODS
Rats with severe contusive SCI were divided into 2 groups: G-CSF group rats were given serial subcutaneous injections of G-CSF, and control group rats (controls) were given only saline injections on postcontusion days 9 to 13. Using the Basso-Beattie-Bresnahan scale and cortical somatosensory evoked potentials, we recorded functional evaluations weekly. The spinal cords were harvested for protein and immunohistochemical analysis, and for electron microscopy examination.


RESULTS
The preserved spinal cord area was larger in G-CSF group rats than in control group rats. Both sensory and motor functions improved after G-CSF treatment. Detachment and disruption of the myelin sheets in the myelinated axons were significantly decreased, and axons sprouted and regenerated. There were fewer microglia and macrophages in the G-CSF group than in the control group. The levels of brain-derived neurotrophic factor were comparable between the 2 groups.


CONCLUSIONS
Delayed G-CSF treatment at the subacute stage of severe contusive SCI promoted spinal cord preservation and improved functional outcomes. The mechanism of G-CSF's protection may be related in part to attenuating the infiltration of microglia and macrophages.
Department of Surgery (Division of Neurosurgery), College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Jung-Shun
JS
Lee
Cheng-Chang
CC
Yang
Yu-Min
YM
Kuo
Chun-I
CI
Sze
Jung-Yu C
JY
Hsu
Yi-Hung
YH
Huang
Shun-Fen
SF
Tzeng
Ching-Lin
CL
Tsai
Hsing-Hong
HH
Chen
I-Ming
IM
Jou
D000818:Animals; D003288:Contusions; D004195:Disease Models, Animal; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation; D013997:Time Factors
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor