title: Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy.
abstract: OBJECTIVE
  Recent studies have emphasized the beneficial effects of the vascular endothelial growth factor (VEGF) on neurone survival and Schwann cell proliferation. VEGF is a potent angiogenic factor, and angiogenesis has long been recognized as an important and necessary step during tissue repair. Here, we investigated the effects of VEGF on sciatic nerve regeneration.
  
  
  METHODS
  Using light and electron microscopy, we evaluated sciatic nerve regeneration after transection and VEGF gene therapy. We examined the survival of the neurones in the dorsal root ganglia and in lumbar 4 segment of spinal cord. We also evaluated the functional recovery using the sciatic functional index and gastrocnemius muscle weight. In addition, we evaluated the VEGF expression by immunohistochemistry.
  
  
  RESULTS
  Fluorescein isothiocyanate-dextran (FITC-dextran) fluorescence of nerves and muscles revealed intense staining in the VEGF-treated group. Quantitative analysis showed that the numbers of myelinated fibres and blood vessels were significantly higher in VEGF-treated animals. VEGF also increased the survival of neurone cell bodies in dorsal root ganglia and in spinal cord. The sciatic functional index and gastrocnemius muscle weight reached significantly higher values in VEGF-treated animals.
  
  
  CONCLUSIONS
  We demonstrate a positive relationship between increased vascularization and enhanced nerve regeneration, indicating that VEGF administration can support and enhance the growth of regenerating nerve fibres, probably through a combination of angiogenic, neurotrophic and neuroprotective effects.
authors.affiliation: Instituto de Ciências Biomédicas, Centro de Ciências da Saúde Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: F R
authors.initials: FR
authors.lastname: Pereira Lopes
authors.forename: B C G
authors.initials: BC
authors.lastname: Lisboa
authors.forename: F
authors.initials: F
authors.lastname: Frattini
authors.forename: F M
authors.initials: FM
authors.lastname: Almeida
authors.forename: M A
authors.initials: MA
authors.lastname: Tomaz
authors.forename: P K
authors.initials: PK
authors.lastname: Matsumoto
authors.forename: F
authors.initials: F
authors.lastname: Langone
authors.forename: S
authors.initials: S
authors.lastname: Lora
authors.forename: P A
authors.initials: PA
authors.lastname: Melo
authors.forename: R
authors.initials: R
authors.lastname: Borojevic
authors.forename: S W
authors.initials: SW
authors.lastname: Han
authors.forename: A M B
authors.initials: AM
authors.lastname: Martinez
mesh_terms: D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A