title: Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury.
abstract: Trauma to the spinal cord creates an initial physical injury damaging neurons, glia, and blood vessels, which then induces a prolonged inflammatory response, leading to secondary degeneration of spinal cord tissue, and further loss of neurons and glia surrounding the initial site of injury. Angiogenesis is a critical step in tissue repair, but in the injured spinal cord angiogenesis fails; blood vessels formed initially later regress. Stabilizing the angiogenic response is therefore a potential target to improve recovery after spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) can initiate angiogenesis, but cannot sustain blood vessel maturation. Platelet-derived growth factor (PDGF) can promote blood vessel stability and maturation. We therefore investigated a combined application of VEGF and PDGF as treatment for traumatic spinal cord injury, with the aim to reduce secondary degeneration by promotion of angiogenesis. Immediately after hemisection of the spinal cord in the rat we delivered VEGF and PDGF and to the injury site. One and 3 months later the size of the lesion was significantly smaller in the treated group compared to controls, and there was significantly reduced gliosis surrounding the lesion. There was no significant effect of the treatment on blood vessel density, although there was a significant reduction in the numbers of macrophages/microglia surrounding the lesion, and a shift in the distribution of morphological and immunological phenotypes of these inflammatory cells. VEGF and PDGF delivered singly exacerbated secondary degeneration, increasing the size of the lesion cavity. These results demonstrate a novel therapeutic intervention for SCI, and reveal an unanticipated synergy for these growth factors whereby they modulated inflammatory processes and created a microenvironment conducive to axon preservation/sprouting.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. c.lutton@qut.edu.au
authors.forename: Cameron
authors.initials: C
authors.lastname: Lutton
authors.forename: Yun Wai
authors.initials: YW
authors.lastname: Young
authors.forename: Richard
authors.initials: R
authors.lastname: Williams
authors.forename: Adrian C B
authors.initials: AC
authors.lastname: Meedeniya
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: Ben
authors.initials: B
authors.lastname: Goss
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A