Src family kinase inhibitor PP1 improves motor function by reducing edema after spinal cord contusion in rats

Abstract

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 PP1 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 intrapcritoneally 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. © Springer-Verlag 2003.