GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury.
OBJECTIVE
This study investigated the effects of granulocyte macrophage-colony stimulating factor (GM-CSF) on the scar formation and repair of spinal cord tissues in rat spinal cord injury (SCI) model.


METHODS
Sprague-Dawley male rats (8 weeks old) were randomly divided into the sham-operated group, spinal cord injury group, and injury with GM-CSF treated group. A spinal cord injury was induced at T9/10 levels of rat spinal cord using a vascular clip. GM-CSF was administrated via intraperitoneal (IP) injection or on the dural surface using Gelfoam at the time of SCI. The morphological changes, tissue integrity, and scar formation were evaluated until 4 weeks after SCI using histological and immunohistochemical analyses.


RESULTS
The administration of GM-CSF either via IP injection or local treatment significantly reduced the cavity size and glial scar formation at 3-4 weeks after SCI. GM-CSF also reduced the expression of core proteins of chondroitin sulfate proteoglycans (CSPGs) such as neurocan and NG2 but not phosphacan. In particular, an intensive expression of glial fibriallary acidic protein (GFAP) and neurocan found around the cavity at 4 weeks was obviously suppressed by GM-CSF. Immunostaining for neurofilament (NF) and Luxol fast blue (LFB) showed that GM-CSF preserved well the axonal arrangement and myelin structure after SCI. The expression of GAP-43, a marker of regenerating axons, also apparently increased in the rostral grey matter by GM-CSF.


CONCLUSIONS
These results suggest that GM-CSF could enhance long-term recovery from SCI by suppressing the glial scar formation and enhancing the integrity of axonal structure.
Huang
Xian
X
Department of Neurosurgery, Inha University College of Medicine, Incheon, Republic of Korea.
Kim
Jin-Mo
JM
Kong
Tae Ho
TH
Park
So Ra
SR
Ha
Yoon
Y
Kim
Moon Hang
MH
Park
Hyeonseon
H
Yoon
Seung Hwan
SH
Park
Hyung Chun
HC
Park
Jong Oon
JO
Min
Byoung-Hyun
BH
Choi
Byung Hyune
BH
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor