title: VEGF-A promotes both pro-angiogenic and neurotrophic capacities for nerve recovery after compressive neuropathy in rats.
abstract: Nerve recovery following injury is usually incomplete, leaving functional deficits. Our aim was to investigate the neural changes in pro-angiogenic, pro-inflammatory and apoptotic factors during and after chronic nerve compression (CNC). Nerve function was impaired after CNC and was progressively restored after nerve decompression, while nerve blood flow was elevated. While the expression of the pro-inflammatory and pro-angiogenic cytokines IL-6, TNF-α and VEGF-A was high during and after CNC, we observed that inhibition of VEGF-A receptors strongly counteracted the angiogenic response induced by the ex vivo CNC. Activation of the pro-survival transcription factor nuclear factor-kappa B (NF-κB) increased during CNC, returning to control levels after nerve decompression. After nerve decompression, the downregulation of Mdm2 correlated well with an increased expression of pro-apoptotic transcription factor p53. All together, we bring novel evidence that CNC activates transcription factors such as NF-κB and p53, which are key effectors of the cellular stress response, suggesting a neuroprotective process associated with an increased VEGF-A-mediated neurotrophic effect. Our results highlight the role of pro-angiogenic and pro-inflammatory cytokines during CNC that are reinforced by increasing neurotrophic capacity during recovery to promote nerve regeneration.
authors.affiliation: IBCP-UMR 5305 CNRS, 7 passage du Vercors, 69 367, Lyon Cedex 07, France, julien.pelletier17@gmail.com.
authors.forename: Julien
authors.initials: J
authors.lastname: Pelletier
authors.forename: Emilie
authors.initials: E
authors.lastname: Roudier
authors.forename: Pierre
authors.initials: P
authors.lastname: Abraham
authors.forename: Bérengère
authors.initials: B
authors.lastname: Fromy
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Saumet
authors.forename: Olivier
authors.initials: O
authors.lastname: Birot
authors.forename: Dominique
authors.initials: D
authors.lastname: Sigaudo-Roussel
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009408:Nerve Compression Syndromes / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D010766:Phosphorylation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D017208:Rats, Wistar; D020127:Recovery of Function; D012039:Regional Blood Flow; D012584:Sciatic Nerve / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D009414:Nerve Growth Factors; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2