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Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury

Lutton, Cameron J., Young, Yun Wai, Williams, Richard, Meedeniya, Adrian C.B., MacKay-Sim, Alan, & Goss, Ben (2012) Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury. Journal of Neurotrauma, 29(5), pp. 957-970.

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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.

Impact and interest:

15 citations in Scopus
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15 citations in Web of Science®

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ID Code: 52861
Item Type: Journal Article
Keywords: axonal injury, degeneration, immunohistochemistry, inflammation, plasma membrane, synaptic loss and deafferentation, traumatic brain injury, vascular reactivity, platelet derived growth factor, vasculotropin, angiogenesis, animal experiment, animal model, animal tissue, article, blood vessel parameters, cell count, controlled study, drug delivery system, gliosis, inflammatory cell, macrophage, male, microglia, nonhuman, phenotype, rat, spinal cord injury, treatment response
DOI: 10.1089/neu.2010.1423
ISSN: 0897-7151
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Schools > School of Civil Engineering & Built Environment
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 01 Aug 2012 08:13
Last Modified: 22 Feb 2013 16:00

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