J Reconstr Microsurg 2011; 27(3): 173-178
DOI: 10.1055/s-0030-1270532
© Thieme Medical Publishers

Vascular Endothelial Growth Factor and Its Receptors Are Expressed in Human Nerve Grafts

Tuija M. Ylä-Kotola1 , Susanna C. Kauhanen1 , Ilmo V. Leivo3 , Caj Haglund2 , Erkki Tukiainen1
  • 1Department of Plastic Surgery, Helsinki University Hospital, HUS
  • 2Department of Surgery, Helsinki University Hospital, HUS
  • 3Department of Pathology, University of Helsinki, Helsinki, Finland
Further Information

Publication History

Publication Date:
21 December 2010 (online)

ABSTRACT

Vascularization and angiogenicity of human nonvascularized nerve grafts in the second stage of facial reanimation were studied. Immunohistochemistry for endothelial markers (CD-31) and vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 was performed on distal end biopsies from 35 cross-facial nerve grafts. In grafted nonvascularized nerve, density of vascular structures (also clearly immunopositive for VEGF and both receptors) showed a mean of 166 vessels (range 78 to 267) per unit area, corresponding to control values. In addition, VEGF was expressed in axons and perineural structures. In control samples, VEGF expression was low and occurred in the myelin sheath. In nerve grafts, expression of Flt-1 and Flk-1 (less intense) was seen in axons and perineural structures. A higher density of vessels was associated with lower VEGF expression (not significant). In short, expression of VEGF and its receptors is described in human nerve grafts and compared with basic histology and p75 nerve growth factor receptor expression of the nerve graft and functional outcome of patients.

REFERENCES

  • 1 Carmeliet P, Storkebaum E. Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders.  Semin Cell Dev Biol. 2002;  13 39-53
  • 2 Senger D R, Galli S J, Dvorak A M, Perruzzi C A, Harvey V S, Dvorak H F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.  Science. 1983;  219 983-985
  • 3 Ferrara N, Henzel W J. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.  Biochem Biophys Res Commun. 1989;  161 851-858
  • 4 Soker S, Takashima S, Miao H Q, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor.  Cell. 1998;  92 735-745
  • 5 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 5731-5740
  • 6 Hobson M I, Green C J, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy.  J Anat. 2000;  197 (Pt 4) 591-605
  • 7 Storkebaum E, Lambrechts D, Carmeliet P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection.  Bioessays. 2004;  26 943-954
  • 8 Oosthuyse B, Moons L, Storkebaum E et al.. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.  Nat Genet. 2001;  28 131-138
  • 9 Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts.  Brain Res. 1999;  846 219-228
  • 10 Islamov R R, Chintalgattu V, Pak E S, Katwa L C, Murashov A K. Induction of VEGF and its Flt-1 receptor after sciatic nerve crush injury.  Neuroreport. 2004;  15 2117-2121
  • 11 Hobson M I, Brown R, Green C J, Terenghi G. Inter-relationships between angiogenesis and nerve regeneration: a histochemical study.  Br J Plast Surg. 1997;  50 125-131
  • 12 Zhang H, Vutskits L, Pepper M S, Kiss J Z. VEGF is a chemoattractant for FGF-2-stimulated neural progenitors.  J Cell Biol. 2003;  163 1375-1384
  • 13 Rovak J M, Mungara A K, Aydin M A, Cederna P S. Effects of vascular endothelial growth factor on nerve regeneration in acellular nerve grafts.  J Reconstr Microsurg. 2004;  20 53-58
  • 14 Harii K. Microneurovascular free muscle transplantation for reanimation of facial paralysis.  Clin Plast Surg. 1979;  6 361-375
  • 15 Ylä-Kotola T M, Kauhanen M SC, Asko-Seljavaara S L, Haglund C H, Tukiainen E, Leivo I V. P75 nerve growth factor receptor is expressed in regenerating human nerve grafts.  J Surg Res. 2008;  146 254-261
  • 16 Ylä-Kotola T M, Kauhanen M SC, Asko-Seljavaara S L. Facial reanimation by transplantation of a microneurovascular muscle: long-term follow-up.  Scand J Plast Reconstr Surg Hand Surg. 2004;  38 272-276
  • 17 Kauhanen S C, Ylä-Kotola T M, Leivo I V, Tukiainen E, Asko-Seljavaara S L. Long-term adaptation of human microneurovascular muscle flaps to the paralyzed face: an immunohistochemical study.  Microsurgery. 2006;  26 557-565
  • 18 Bancroft J D, Stevens A. A Theory and Practice of Histological Techniques. 1st ed. Edinburgh: Churchill Livingstone; 1977: 40
  • 19 Jaraj S J, Camparo P, Boyle H et al.. Intra- and interobserver reproducibility of interpretation of immunohistochemical stains of prostate cancer.  Virchows Arch. 2009;  455 375-381
  • 20 Madsen J E, Wang J-S, Hukkanen M et al.. Sensory nerve ingrowth during bone graft incorporation in the rat.  Acta Orthop Scand. 1996;  67 217-220
  • 21 Ylä-Kotola T M, Kauhanen M S, Koskinen S K, Asko-Seljavaara S L. Magnetic resonance imaging of microneurovascular free muscle flaps in facial reanimation.  Br J Plast Surg. 2005;  58 22-27
  • 22 Schultes G, Gaggl A, Kleinert R, Kärcher H. Vascularized versus non-vascularized nerve transfers: histologic study in rats.  J Reconstr Microsurg. 2001;  17 637-642
  • 23 Koshima I, Harii K. Experimental study of vascularized nerve grafts: morphometric study of axonal regeneration of nerves transplanted into silicone tubes.  Ann Plast Surg. 1985;  14 235-243
  • 24 Sondell M, Sundler F, Kanje M. Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk-1 receptor.  Eur J Neurosci. 2000;  12 4243-4254
  • 25 Akhavani M A, Sivakumar B, Paleolog E M, Kang N. Angiogenesis and plastic surgery.  J Plast Reconstr Aesthet Surg. 2008;  61 1425-1437
  • 26 Boyd J G, Gordon T. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury.  Mol Neurobiol. 2003;  27 277-324
  • 27 Schmidt C E, Leach J B. Neural tissue engineering: strategies for repair and regeneration.  Annu Rev Biomed Eng. 2003;  5 293-347

Susanna C KauhanenM.D. Ph.D. 

P.O. Box 266

00029 HUS, Finland

Email: susanna.kauhanen@hus.fi

    >