Delayed administration of a bio-engineered zinc-finger VEGF-A gene therapy is neuroprotective and attenuates allodynia following traumatic spinal cord injury

Following spinal cord injury (SCI) there are drastic changes that occur in the spinal microvasculature, including ischemia, hemorrhage, endothelial cell death and blood-spinal cord barrier disruption. Vascular endothelial growth factor-A (VEGF-A) is a pleiotropic factor recognized for its pro-angiog...

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Bibliographic Details
Published in:PloS one 2014-05, Vol.9 (5), p.e96137-e96137
Main Authors: Figley, Sarah A, Liu, Yang, Karadimas, Spyridon K, Satkunendrarajah, Kajana, Fettes, Peter, Spratt, S Kaye, Lee, Gary, Ando, Dale, Surosky, Richard, Giedlin, Martin, Fehlings, Michael G
Format: Article
Language:English
Subjects:
Adenoviridae
Analysis
Angiogenesis
Animals
Apoptosis
Bioengineering
Biology and Life Sciences
Blood
Blood vessels
Brain research
Cell death
Compression
Diabetic neuropathy
Endothelial cells
Female
Gene expression
Gene therapy
Genes
Genetic Therapy - methods
Health care networks
HEK293 Cells
Hemorrhage
Humans
Hyperalgesia - etiology
Hyperalgesia - metabolism
Hyperalgesia - pathology
Hyperalgesia - therapy
Immunosuppression
Injuries
Ischemia
Isoforms
Medicine and Health Sciences
Microvasculature
Neovascularization, Physiologic - genetics
Neuroprotection
Neurosciences
Pain
Pain perception
Paralysis
Preservation
Proteins
Rats
Rats, Wistar
RecA protein
Recovery of function
Research and Analysis Methods
Rodents
Spinal cord
Spinal cord injuries
Spinal Cord Injuries - complications
Spinal Cord Injuries - metabolism
Spinal Cord Injuries - pathology
Spinal Cord Injuries - therapy
Spinal cord injury
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - biosynthesis
Vascular Endothelial Growth Factor A - genetics
Vectors (Biology)
Windows (intervals)
Zinc
Zinc finger proteins
Zinc Fingers
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Summary:Following spinal cord injury (SCI) there are drastic changes that occur in the spinal microvasculature, including ischemia, hemorrhage, endothelial cell death and blood-spinal cord barrier disruption. Vascular endothelial growth factor-A (VEGF-A) is a pleiotropic factor recognized for its pro-angiogenic properties; however, VEGF has recently been shown to provide neuroprotection. We hypothesized that delivery of AdV-ZFP-VEGF--an adenovirally delivered bio-engineered zinc-finger transcription factor that promotes endogenous VEGF-A expression--would result in angiogenesis, neuroprotection and functional recovery following SCI. This novel VEGF gene therapy induces the endogenous production of multiple VEGF-A isoforms; a critical factor for proper vascular development and repair. Briefly, female Wistar rats--under cyclosporin immunosuppression--received a 35 g clip-compression injury and were administered AdV-ZFP-VEGF or AdV-eGFP at 24 hours post-SCI. qRT-PCR and Western Blot analysis of VEGF-A mRNA and protein, showed significant increases in VEGF-A expression in AdV-ZFP-VEGF treated animals (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0096137