An acute growth factor treatment that preserves function after spinal cord contusion injury

Abstract

Inflammation of the spinal cord after traumatic spinal cord injury (SCI) leads to destruction of healthy tissue. This "secondary degeneration" is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study, we showed that combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor, significantly reduced secondary degeneration after hemisection injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30 days, compared to control animals, and further reduced the cavity at 90 days in treated animals, whereas in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behavior after spinal contusion injury, a more relevant pre-clinical model of SCI. The growth factors were delivered for the first 7 days to the injury site by osmotic minipump. Locomotor behavior was monitored at 1-28 days after injury using the Basso, Beattie and Bresnahan (BBB) score and at 30 days using automated gait analysis. Treated animals had BBB scores of 18; control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.

Keywords: PDGF; VEGF; neural protection; neuroinflammation; spinal cord injury.