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.

Harvest site influences the growth properties of adipose derived stem cells

“…In this study we decided to use bFGF and PDGF as they are potent mitogens for glial cells and have a potential effect on nerve repair (Lutton et al 2012;Yun et al 2010). Fibroblast growth factors (FGFs) have shown potential effects on the repair and regeneration of a wide spectrum of tissues, including skin, blood vessel, muscle (Tassi et al 2011), de novo adipogenesis (Tabata et al 2000), tendon/ligament (Hankemeier et al 2005), cartilage (Martin et al 2001), bone (Kimura et al 2008), tooth (Kitamura et al 2011), and nerve tissues (Yun et al 2010).…”

Medical and Surgical Management after Spinal Cord Injury: Vasopressor Usage, Early Surgerys, and Complications

“…1,2 In the past several years there has been a surge of interest in medical treatment standards to prevent secondary injury and optimize the cord for potential recovery. [3][4][5][6] The optimization of spinal cord perfusion is thought to play a critical role in the prevention of secondary injury. 4,6 Ischemia of the cord becomes progressively worse over the first several hours after injury.…”

“…4,6 Ischemia of the cord becomes progressively worse over the first several hours after injury. [3][4][5][6] Although prevention of hypotension is recommended based on traumatic brain injury (TBI) data, 7 there is an additional thought that raising mean arterial blood pressure above normal levels would provide further perfusion to injured axons and improve outcome. 8,9 In 2008 the Consortium for Spinal Cord Medicine introduced their 10th clinical practice guideline: Early Acute Management in Adults with SCI.…”

Therapeutic Potential of Paracrine Factors and Secretome-based Treatment in Spinal Cord Injury

“…Accordingly, therapy based on single factors failed to deliver satisfying results in a multitude of pre-clinical and clinical studies. Even negative effects of single-molecule treatment were reported, which was reversible when a combination of factors was administered [33,34] . With negative long-term results and a growing list of reported complications, cortisol treatment regimens are current topic of controversial discussion [35] .…”