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

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 upregulated in an in vitro model of PD using the neurotoxin rotenone. Addition of exogenous VEGF-B-167 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 3 mu g VEGF-B-186, the more diffusible VEGF-B isoform, in a mild progressive unilateral 6-hydroxydopamine (6-OHDA) rat in vivo PD model. Treatment with VEGF-B-186 6 h 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-B-186 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-B-186 could be a new candidate trophic factor for the treatment of PD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.