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

Molecular Neurobiology - Tập 51 - Trang 240-251 - 2014
Julien Pelletier1,2,3, Emilie Roudier3, Pierre Abraham4, Bérengère Fromy1,2, Jean Louis Saumet1,2, Olivier Birot3, Dominique Sigaudo-Roussel1,2
1IBCP–UMR 5305 CNRS, Lyon Cedex 07, France
2University of Lyon 1, Lyon Cedex 07, France
3Faculty of health, angiogenesis research group, York University, Toronto, Canada.
4Laboratory of Vascular Investigations, University Hospital of Angers, Angers, France

Tóm tắt

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.

Tài liệu tham khảo

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