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

Autor: Peter Fettes, Yang Liu, Dale Ando, Martin Giedlin, Gary Lee, Spyridon K. Karadimas, S. Kaye Spratt, Kajana Satkunendrarajah, Sarah A. Figley, Richard T. Surosky, Michael G. Fehlings
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Vascular Endothelial Growth Factor A
Critical Care and Emergency Medicine
Angiogenesis
Hindlimb
Nervous System
Molecular Cell Biology
Medicine and Health Sciences
Spinal Cord Injury
Spinal cord injury
Trauma Medicine
Mammals
Multidisciplinary
Cell Death
Zinc Fingers
Genomics
Gene Therapy
Animal Models
Vascular endothelial growth factor A
Allodynia
medicine.anatomical_structure
Spinal Cord
Neurology
Cell Processes
Hyperalgesia
Anesthesia
Vertebrates
Medicine
Female
Anatomy
medicine.symptom
Research Article
Blood vessel
medicine.medical_specialty
Science
Central nervous system
Neovascularization
Physiologic
Research and Analysis Methods
Rodents
Neuroprotection
Spinal Cord Diseases
Adenoviridae
Model Organisms
Genomic Medicine
Internal medicine
Genetics
medicine
Animals
Humans
Rats
Wistar
Molecular Biology Techniques
Molecular Biology
Spinal Cord Injuries
Clinical Genetics
business.industry
Organisms
Biology and Life Sciences
Cell Biology
Genetic Therapy
medicine.disease
Rats
Neuroanatomy
HEK293 Cells
Endocrinology
business
Neuroscience
Zdroj: PLoS ONE, Vol 9, Iss 5, p e96137 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: 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
Databáze: OpenAIRE
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