J Reconstr Microsurg 2001; 17(8): 625-630
DOI: 10.1055/s-2001-18818
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Neurogenic Perspective on Vascular Endothelial Growth Factor: Review of the Literature

Romed Meirer, Raffi Gurunluoglu, Maria Siemionow
  • Microsurgery Laboratory, Department of Plastic and Reconstructive Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
Further Information

Publication History

Publication Date:
05 December 2001 (online)

ABSTRACT

Among a variety of approaches used to stimulate nerve regeneration in experimental settings, is the use of a class of proteins designated as nerve growth factors and various other growth factors. Of these, vascular endothelial growth factor (VEGF), has been demonstrated to possess a potential to stimulate nerve regeneration in addition to its angiogenic properties. A number of studies have investigated the role of VEGF in nerve regeneration, demonstrating that it has both neurogenic and mitogenic activity on cells in the peripheral nervous system. It is therefore likely that VEGF is a molecule of major significance for nerve homeostasis, especially during development, and possibly after nerve injury. This paper reviews the mechanisms of VEGF signal transduction in neurogenesis, and focuses on recent studies that have considerably widened the understanding of the way in which VEGF affects peripheral nerve regeneration. By emphasizing the possible therapeutic implication of VEGF in nerve pathology, the authors would like to introduce a new research approach to study the role of VEGF in the nervous system. They believe that in the future, the factor might become a powerful tool in enhancing nerve regeneration in clinical practice.

REFERENCES

  • 1 Santos F, Bilbao G, Rodrigo J. Experimental model for local administration of nerve growth factor in microsurgical nerve reconnections.  Microsurgery . 1995;  16 71
  • 2 Gimenez Y, Ribotta M, Revah F. Prevention of motoneuron death by adenovirus-mediated neurotrophic factors.  J Neurosci Res . 1997;  48 281
  • 3 Kim D H, Gutin P H, Noble L J. Treatment with genetically engineered fibroblasts producing NGF or BDNF can accelerate recovery from traumatic spinal cord injury in the adult rat.  Neuroreport . 1996;  7 2221
  • 4 Moir M S, Wang M Z, To M. Delayed repair of transected nerves: effect of brain-derived neurotrophic factor.  Arch Otolarnygol Head Neck Surg . 2000;  126 501
  • 5 Newman J P, Verity A N, Hawatmeh S. Ciliary neurotrophic factor enhances peripheral nerve regeneration.  Arch Otolaryngol Head Neck . 1996;  122 399
  • 6 Lewin S L, Utley D S, Cheng E T. Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone.  Laryngoscope . 1997;  107 992
  • 7 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.  Endocr Rev . 1997;  18 4
  • 8 Poltorak Z, Cohen T, Sivan R. VEGF 145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix.  J Biol Chem . 1997;  272 7151
  • 9 De Vries C, Escobedo J A, Ueno H. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.  Science . 1992;  255 989
  • 10 Quinn T P, Peters K G, De Vries C. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.  Proc Natl Acad Sci USA . 1993;  90 7533
  • 11 Waltenberger J, Claessonwelsh L, Siegbahn A. Different signal transduction properties of KDR and flt1, two receptors for vascular endothelial growth factor.  J Biol Chem . 1994;  269 26988
  • 12 Yoshida A, Anand-Apte B, Zetter B R. Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor.  Growth Factors . 1996;  13 57
  • 13 Soker S, Fidder H, Neufeld G, Klagsbrun M. Characterization of novel VEGF binding proteins associated with tumor cells that bind VEGF165 but not VEGF121 .  J Biol Chem . 1996;  271 5761
  • 14 Kitsukawa T, Shimizu M, Sanbo M. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice.  Neuron . 1997;  19 995
  • 15 Sondell M, Kanje M. Postnatal expression of VEGF and its receptor flk-1 in peripheral ganglia.  Neuroreport . 2001;  12 105
  • 16 Kawasaki T, Kitsukawa T, Bekku Y. Requirement for neuropilin-1 in embryonic vessel formation.  Development . 1999;  126 4895
  • 17 Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system.  J Neurosci . 1999;  19 5731
  • 18 Samii A, Unger W, Lange W. Vascular endothelial growth factor in peripheral nerve and dorsal root ganglia in diabetic neuropathy in rats.  Neurosci Lett . 1999;  262 159
  • 19 Schratzberger P, Schratzberger G, Silver M. Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy.  Nature Med . 2000;  6 405
  • 20 Ferrara N, Carevermoore K, Chen H. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.  Nature . 1996;  380 439
  • 21 Shalaby F, Rossant J, Yamaguchi T P. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.  Nature . 1995;  376 62
  • 22 Hobson M I, Green C J, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy.  J Anat . 2000;  4 591
  • 23 Schratzberger P, Walter D H, Rittig K. Reversal of experimental diabetic neuropathy by VEGF gene transfer.  J Clin Invest . 2001;  107 1083
  • 24 Simovic D, Isner J M, Ropper A H. Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia.  Arch Neurol . 2001;  58 761
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