Src family kinase inhibitor PP1 improves motor function by reducing edema after spinal cord contusion in rats.
Following spinal cord injury vascular permeability increases around the area of injury, which possibly leads to secondary tissue damage. Vascular endothelial growth factor (VEGF) and Src which exists downstream of VEGF may contribute to edema formation. We here report that the Src family kinase inhibitor PPI could reduce edema and the inflammatory response after spinal cord injury. In this study we have examined the effect of PPI on motor function after mild spinal cord compression injury. We utilized a mild spinal cord compression model in rats. PPI or vehicle only was administered intraperitoneally after cord compression. The motor function of the hind limbs after injury was categorized into 7 grades. At 1, 3, 7 and 14 days after injury, the spinal cord was removed and the extent of edema formation and inflammation were examined using immunohistochemistry with an anti-IgG and anti-ED-1 antibody. The immunohistochemical analysis revealed that the area of edema formation and inflammation was remarkably reduced in animals with PPI. The muscle function was flaccid in both groups immediately after injury. However, at 3 and 8 days after injury, a significant improvement was observed in the PPI group. These results suggest that PPI is a strong candidate for drug treatment of spinal cord injury.
Akiyama
C
C
Department of Neurosurgery, Osaka University Medical School, Suita, Osaka, Japan. cakiyama@nsurg.med.osaka-u.ac.jp
Yuguchi
T
T
Nishio
M
M
Fujinaka
T
T
Taniguchi
M
M
Nakajima
Y
Y
Yoshimine
T
T
D000818:Animals; D053331:Ectodysplasins; D004487:Edema / Q000209:etiology* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism; D013117:Spinal Cord Compression / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D053331:Ectodysplasins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D042461:Vascular Endothelial Growth Factor A; D019061:src-Family Kinases