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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Elisabet Ohlin
  • Veronica Francardo
  • Hanna Lindgren
  • Stephanie E Sillivan
  • Sean S O'Sullivan
  • Andrew S Luksik
  • Fair M Vassoler
  • Andrew J Lees
  • Christine Konradi
  • Angela Cenci Nilsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Pages (from-to)2339-2357
JournalBrain
Volume134
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Related research output

Elisabet Ohlin, 2011, Basal Ganglia Pathophysiology Unit. 68 p.

Research output: ThesisDoctoral Thesis (compilation)

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