Vascular endothelial growth factor-B is neuroprotective in an in vivo rat model of Parkinson's disease

Torsten Falk, Xu Yue, Shiling Zhang, Alexander D. McCourt, Brandon J. Yee, Robert T. Gonzalez, Scott J. Sherman

Research output: Contribution to journalArticle

Abstract

Developing novel neuroprotective strategies for the treatment of Parkinson's disease (PD) is of great importance. We have previously shown that vascular endothelial growth factor-B (VEGF-B) is up-regulated in an in vitro model of PD using the neurotoxin rotenone. Addition of exogenous VEGF-B167 was neuroprotective in this same model, suggesting that VEGF-B is a natural response to neurodegenerative challenges. Now we have extended this research using in vivo experiments. We tested a single intra-striatal injection of 3μg VEGF-B186, the more diffusible VEGF-B isoform, in a mild progressive unilateral 6-hydroxydopamine (6-OHDA) rat in vivo PD model. Treatment with VEGF-B186 6h prior to lesioning with 6-OHDA improved amphetamine-induced rotations and forepaw preference at 2, 4 and 6 weeks post-injection, indicating a neuroprotective effect. Immunohistochemical analysis showed that VEGF-B186 treatment partially protected dopaminergic fibers in the striatum and demonstrated a partial rescue of the dopaminergic neurons in the caudal sub-region of the substantia nigra. Altogether our data suggest that VEGF-B186 could be a new candidate trophic factor for the treatment of PD.

Original languageEnglish (US)
Pages (from-to)43-47
Number of pages5
JournalNeuroscience Letters
Volume496
Issue number1
DOIs
StatePublished - May 27 2011
Externally publishedYes

Keywords

  • 6-OHDA lesion
  • Midbrain culture
  • Neurotrophic therapy
  • VEGF-B167
  • VEGF-B186

ASJC Scopus subject areas

  • Neuroscience(all)

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