VEGF-A promotes both pro-angiogenic and neurotrophic capacities for nerve recovery after compressive neuropathy in rats.
Mol Neurobiol
; 51(1): 240-51, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-24865514
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nervo Isquiático
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Neovascularização Fisiológica
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Recuperação de Função Fisiológica
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Fator A de Crescimento do Endotélio Vascular
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Síndromes de Compressão Nervosa
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Fatores de Crescimento Neural
Limite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article