VEGF165 therapy exacerbates secondary damage following spinal cord injury.
Vascular endothelial growth factor (VEGF) demonstrates potent and well-characterized effects on endothelial cytoprotection and angiogenesis. In an attempt to preserve spinal microvasculature and prolong the endogenous neovascular response observed transiently following experimental spinal cord injury (SCI), exogenous recombinant human VEGF (rhVEGF165) was injected into the injured rat spinal cord. Adult female Fischer 344 rats were subjected to moderate SCI (12.5 g-cm) using the NYU impactor. At 72 h after injury, animals were randomly assigned to three experimental groups receiving no microinjection or injection of saline or saline containing 2 microg of rhVEGF165. Acutely, VEGF injection resulted in significant microvascular permeability and infiltration of leukocytes into spinal cord parenchyma. 6 weeks postinjection, no significant differences were observed in most measures of microvascular architecture following VEGF treatment, but analysis of histopathology in spinal cord tissue revealed profound exacerbation of lesion volume. These results support the idea that intraparenchymal application of the proangiogenic factor VEGF may exacerbate SCI, likely through its effect on vessel permeability.
The Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
Richard L
RL
Benton
Scott R
SR
Whittemore
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D005260:Female; D006801:Humans; D008833:Microcirculation / Q000187:drug effects* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*; D020758:Spinal Cord Vascular Diseases / Q000209:etiology* / Q000473:pathology*; D013904:Thoracic Vertebrae / Q000098:blood supply / Q000187:drug effects / Q000293:injuries; D014022:Tissue Survival / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000009:adverse effects*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A