Title: Neutralizing Endogenous VEGF Following Traumatic Spinal Cord Injury Modulates Microvascular Plasticity but not Tissue Sparing or Functional Recovery
Volume: 6
Issue: 2
Author(s): Richard L. Benton, Melissa A. Maddie, Mark J. Gruenthal, Theo Hagg and Scott R. Whittemore
Affiliation:
Keywords:
VEGF Trap, Aflibercept, intravital lectin, neovascularization, endothelial, Basso Mouse Scale for Locomotion (BMS)
Abstract: Acute loss of spinal cord vascularity followed by an endogenous adaptive angiogenic response with concomitant microvascular dysfunction is a hallmark of traumatic spinal cord injury (SCI). Recently, the potent vasoactive factor vascular endothelial growth factor (VEGF) has received much attention as a putative therapeutic for the treatment of various neurodegenerative disorders, including SCI. Exogenous VEGF exerts both protective and destabilizing effects on microvascular elements and tissue following SCI but the role of endogenous VEGF is unclear. In the present study, we systemically applied a potent and well characterized soluble VEGF antagonist to adult C57Bl/6 mice post-SCI to elucidate the relative contribution of VEGF on the acute evolving microvascular response and its impact on functional recovery. While the VEGF Trap did not alter vascular density in the injury epicenter or penumbra, an overall increase in the number of Griffonia simplicifolia isolectin-B4 bound microvessels was observed, suggesting a VEGFdependency to more subtle aspects of endothelial plasticity post-SCI. Neutralizing endogenous VEGF neither attenuated nor exacerbated chronic histopathology or functional recovery. These results support the idea that overall, endogenous VEGF is not neuroprotective or detrimental following traumatic SCI. Furthermore, they suggest that angiogenesis in traumatically injured spinal tissue is regulated by multiple effectors and is not limited by endogenous VEGF activation of affected spinal microvessels.
