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Molecular Neurobiology

, Volume 51, Issue 1, pp 240–251 | Cite as

VEGF-A Promotes Both Pro-angiogenic and Neurotrophic Capacities for Nerve Recovery After Compressive Neuropathy in Rats

  • Julien PelletierEmail author
  • Emilie Roudier
  • Pierre Abraham
  • Bérengère Fromy
  • Jean Louis Saumet
  • Olivier Birot
  • Dominique Sigaudo-Roussel
Article

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.

Keywords

Chronic nerve compression Nerve recovery VEGF-A Pro-inflammatory factor Nerve blood flow 

Notes

Acknowledgments

This study was funded by ANR grant ANR-07-SEST-01601. Julien Pelletier was supported by a grant from the French Ministère de l’Enseignement Supérieur et de la Recherche (University of Lyon 1, EDISS) and by a grant from the Rhônes-Alpes Region (CMIRA EXPLORA’DOC 2009). Research in the Angiogenesis Research Group is funded by the Natural Sciences and Engineering Research Council of Canada (NSERC DG 341258-2011 to Olivier Birot). We thank Mrs. Patricia Hulmes for editorial assistance. We would like to thank Virginie Briffaud for help assistance in manuscript.

Conflict of Interest Statement

No author has any conflict of interest related to the content of this paper.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Julien Pelletier
    • 1
    • 2
    • 3
    Email author
  • Emilie Roudier
    • 3
  • Pierre Abraham
    • 4
  • Bérengère Fromy
    • 1
    • 2
  • Jean Louis Saumet
    • 1
    • 2
  • Olivier Birot
    • 3
  • Dominique Sigaudo-Roussel
    • 1
    • 2
  1. 1.IBCP–UMR 5305 CNRSLyon Cedex 07France
  2. 2.University of Lyon 1Lyon Cedex 07France
  3. 3.Faculty of Health, Angiogenesis Research GroupYork UniversityTorontoCanada
  4. 4.Laboratory of Vascular InvestigationsUniversity Hospital of AngersAngersFrance

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