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Vascular Endothelial Growth Factor (VEGF) and Peripheral Nerve Regeneration

Sondell, Mariann LU (2000)
Abstract
This thesis concerns vascular endothelial growth factor (VEGF) and its possible role as a neurotrophic factor. I have investigated the effect of VEGF on neurons in culture but also in vivo, following a crush lesion of the sciatic nerve, and following nerve repair. Attempts were also made to unravel the mechanism by which VEGF affects neurons and Schwann cells, using a pharmacological approach in combination with techniques like tissue culture, BrdU-labelling, in situ hybridization, immunocytochemistry, image analysis, SDS-PAGE and Western blotting. I found that VEGF stimulates axonal outgrowth from dorsal root (DRG)- and superior cervical ganglia (SCG) through activation of the flk-1 receptor and the MAPK pathway, and that activation of... (More)
This thesis concerns vascular endothelial growth factor (VEGF) and its possible role as a neurotrophic factor. I have investigated the effect of VEGF on neurons in culture but also in vivo, following a crush lesion of the sciatic nerve, and following nerve repair. Attempts were also made to unravel the mechanism by which VEGF affects neurons and Schwann cells, using a pharmacological approach in combination with techniques like tissue culture, BrdU-labelling, in situ hybridization, immunocytochemistry, image analysis, SDS-PAGE and Western blotting. I found that VEGF stimulates axonal outgrowth from dorsal root (DRG)- and superior cervical ganglia (SCG) through activation of the flk-1 receptor and the MAPK pathway, and that activation of the same receptor on Schwann cells results in a proliferative response. VEGF also promotes survival of neurons and satellite cells. We suggest that VEGF acts both by auto- and paracrine mechanisms in the peripheral nervous system, considering the expression of VEGF and flk-1 in cells of DRG, SCG and the sciatic nerve. My second approach was to develop a cell-free nerve graft which could be used for nerve repair. The idea was that by removing the cells from the graft but maintaining the basal lamina the rejection process could be suppressed while regeneration was enhanced. I could show that nerve grafts made acellular by chemical extraction supported regeneration of nerve fibers when transplanted into a defect in the sciatic nerve of recipient rats of a different rat strain. In this system VEGF treatment promoted both vascularization and migration of Schwann cells in the graft, suggesting that for nerve repair VEGF treatment could be beneficial since it stimulates two important aspects of the regeneration process i.e. Schwann cell invasion and neovascularization. Taken together my work lend strong support to our hypothesis that VEGF is a neurotrophic factor, a finding which can have implications for our understanding of nerve injuries. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Prof Brundin, Patrik, Wallenberg Neuroscience Centre, Lund, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Schwann cell, SCG, rat, peripheral nerve regeneration, neuropilin-1, nerve repair, mouse, growth factor, flk-1, axonal outgrowth, DRG, VEGF, Animal physiology, Djurfysiologi
pages
150 pages
publisher
Department of Animal Physiology, Lund University
defense location
The lecture hall, Dept. of Animal Physiology
defense date
2000-12-08 10:15
external identifiers
  • Other:ISRN: LUNBDS/(NBZF/1055)/1-49(2000)
ISBN
91-7874-088-6
language
English
LU publication?
yes
id
59d64be0-c6ce-450d-a0a6-45d7147fc259 (old id 41086)
date added to LUP
2007-08-01 09:00:09
date last changed
2016-09-19 08:45:08
@misc{59d64be0-c6ce-450d-a0a6-45d7147fc259,
  abstract     = {This thesis concerns vascular endothelial growth factor (VEGF) and its possible role as a neurotrophic factor. I have investigated the effect of VEGF on neurons in culture but also in vivo, following a crush lesion of the sciatic nerve, and following nerve repair. Attempts were also made to unravel the mechanism by which VEGF affects neurons and Schwann cells, using a pharmacological approach in combination with techniques like tissue culture, BrdU-labelling, in situ hybridization, immunocytochemistry, image analysis, SDS-PAGE and Western blotting. I found that VEGF stimulates axonal outgrowth from dorsal root (DRG)- and superior cervical ganglia (SCG) through activation of the flk-1 receptor and the MAPK pathway, and that activation of the same receptor on Schwann cells results in a proliferative response. VEGF also promotes survival of neurons and satellite cells. We suggest that VEGF acts both by auto- and paracrine mechanisms in the peripheral nervous system, considering the expression of VEGF and flk-1 in cells of DRG, SCG and the sciatic nerve. My second approach was to develop a cell-free nerve graft which could be used for nerve repair. The idea was that by removing the cells from the graft but maintaining the basal lamina the rejection process could be suppressed while regeneration was enhanced. I could show that nerve grafts made acellular by chemical extraction supported regeneration of nerve fibers when transplanted into a defect in the sciatic nerve of recipient rats of a different rat strain. In this system VEGF treatment promoted both vascularization and migration of Schwann cells in the graft, suggesting that for nerve repair VEGF treatment could be beneficial since it stimulates two important aspects of the regeneration process i.e. Schwann cell invasion and neovascularization. Taken together my work lend strong support to our hypothesis that VEGF is a neurotrophic factor, a finding which can have implications for our understanding of nerve injuries.},
  author       = {Sondell, Mariann},
  isbn         = {91-7874-088-6},
  keyword      = {Schwann cell,SCG,rat,peripheral nerve regeneration,neuropilin-1,nerve repair,mouse,growth factor,flk-1,axonal outgrowth,DRG,VEGF,Animal physiology,Djurfysiologi},
  language     = {eng},
  pages        = {150},
  publisher    = {ARRAY(0x8210358)},
  title        = {Vascular Endothelial Growth Factor (VEGF) and Peripheral Nerve Regeneration},
  year         = {2000},
}