Endothelial proliferation and increased blood-brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia

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  • Jenny E. Westin, Lunds Universitet
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  • Hanna S. Lindgren, Lunds Universitet
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  • Jonathan Gardi, Stereology and Electron Microscopy Laboratory
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  • Jens Randel Nyengaard
  • Patrik Brundin, Lunds Universitet
  • ,
  • Paul Mohapel, Lunds Universitet
  • ,
  • M. Angela Cenci, Lunds Universitet, Biomedical Center F11

3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with molecular and synaptic plasticity in the basal ganglia, but the occurrence of structural remodeling through cell genesis has not been explored. In this study, rats with 6-hydroxydopamine lesions received injections of the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) concomitantly with L-DOPA for 2 weeks. A large number of BrdU-positive cells were found in the striatum and its output structures (globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata) in L-DOPA-treated rats that had developed dyskinesia. The vast majority (60-80%) of the newborn cells stained positively for endothelial markers. This endothelial proliferation was associated with an upregulation of immature endothelial markers (nestin) and a downregulation of endothelial barrier antigen on blood vessel walls. In addition, dyskinetic rats exhibited a significant increase in total blood vessel length and a visible extravasation of serum albumin in the two structures in which endothelial proliferation was most pronounced (substantia nigra pars reticulata and entopeduncular nucleus). The present study provides the first evidence of angiogenesis and blood-brain barrier dysfunction in an experimental model of L-DOPA-induced dyskinesia. These microvascular changes are likely to affect the kinetics of L-DOPA entry into the brain, favoring the occurrence of motor complications.

Original languageEnglish
JournalJournal of Neuroscience
Volume26
Issue37
Pages (from-to)9448-9461
Number of pages14
ISSN0270-6474
DOIs
Publication statusPublished - 13 Sep 2006

    Research areas

  • 6-OHDA, Angiogenesis, Basal ganglia, Blood-brain barrier, BrdU, Dyskinesia, Parkinson's disease, Proliferation

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