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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2058458
- author
- 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
- organization
- publishing date
- 2011
- 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
- pmid:21771855
- 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
- 2016-04-04 07:55:17
- date last changed
- 2022-03-15 07:35:57
@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}},
doi = {{10.1093/brain/awr165}},
volume = {{134}},
year = {{2011}},
}