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Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.

Ohlin, Elisabet LU ; Francardo, Veronica LU ; Lindgren, Hanna LU ; Sillivan, Stephanie E; O'Sullivan, Sean S; Luksik, Andrew S; Vassoler, Fair M; Lees, Andrew J; Konradi, Christine and Cenci Nilsson, Angela LU (2011) In Brain 134. p.2339-2357
Abstract
Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of... (More)
Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain
volume
134
pages
2339 - 2357
publisher
Oxford University Press
external identifiers
  • wos:000294067700019
  • pmid:21771855
  • scopus:80052013736
ISSN
1460-2156
DOI
10.1093/brain/awr165
language
English
LU publication?
yes
id
7878f1e9-8c72-41b1-8e93-de39a0715993 (old id 2058458)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21771855?dopt=Abstract
date added to LUP
2011-08-01 14:21:00
date last changed
2017-05-28 04:32:47
@article{7878f1e9-8c72-41b1-8e93-de39a0715993,
  abstract     = {Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease.},
  author       = {Ohlin, Elisabet and Francardo, Veronica and Lindgren, Hanna and Sillivan, Stephanie E and O'Sullivan, Sean S and Luksik, Andrew S and Vassoler, Fair M and Lees, Andrew J and Konradi, Christine and Cenci Nilsson, Angela},
  issn         = {1460-2156},
  language     = {eng},
  pages        = {2339--2357},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.},
  url          = {http://dx.doi.org/10.1093/brain/awr165},
  volume       = {134},
  year         = {2011},
}