Intrathecally injected granulocyte colony-stimulating factor produced neuroprotective effects in spinal cord ischemia via the mitogen-activated protein kinase and Akt pathways.
Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic factor. Recently, this factor has been shown to exhibit neuroprotective effects on many CNS injuries. Spinal cord ischemic injury that frequently results in paraplegia is a major cause of morbidity after thoracic aorta operations. In the present study, we examined the neuroprotective role of G-CSF on spinal cord ischemia-induced neurological dysfunctions and changes in the mitogen-activated protein kinase (MAPK) and Akt signaling pathways in the spinal cord. Spinal cord ischemia was induced in male Wistar rats by occluding the descending aorta with a 2F Fogarty catheter for 12 min 30 s. Immediately after ischemia surgery, the rats were administered G-CSF (10 mug) or saline by intrathecal (i.t.) injection. The rats were divided into four groups: control, ischemia plus saline, ischemia plus G-CSF and G-CSF alone. The neurological dysfunctions were assessed by calculating the motor deficit index after ischemia surgery. The expressions of MAPK and Akt were studied using Western blotting and double immunohistochemistry. First, we observed that ischemia plus i.t. G-CSF can significantly reduce the motor function defects and downregulate phospho-p38 and phospho-c-Jun N-terminal kinase protein expressions-this can be compared with the ischemia plus saline group. In addition, G-CSF inhibited the ischemia-induced activation of p38 in the astrocytes. Furthermore, we concluded that i.t. G-CSF produced a significant increase in phospho-Akt and phospho-ERK in the motor neurons and exhibited beneficial effects on the spinal cord ischemia-induced neurological defects.
Chen
W-F
WF
Department of Neurosurgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
Jean
Y-H
YH
Sung
C-S
CS
Wu
G-J
GJ
Huang
S-Y
SY
Ho
J-T
JT
Su
T-M
TM
Wen
Z-H
ZH
D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010291:Paresis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases