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

Westin, Jenny LU ; Lindgren, Hanna LU ; Gardi, Jonathan ; Nyengaard, Jens Randel ; Brundin, Patrik LU ; Mohapel, Paul LU and Cenci Nilsson, Angela LU (2006) In J Neurosci 26(37). p.9448-9461
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
basal ganglia, blood-brain barrier, 6-OHDA, angiogenesis, proliferation, BrdU, Parkinson's disease, dyskinesia
in
J Neurosci
volume
26
issue
37
pages
9448 - 9461
publisher
Society for Neuroscience
external identifiers
  • pmid:16971529
  • wos:000240495500013
  • scopus:33748711640
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0944-06.2006
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Basal Ganglia (013212026), Wallenberg Neuroscience Centre, Lund (0131000110)
id
47938515-1216-4076-bac7-b7abfb9d0dab (old id 160996)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16971529&dopt=Abstract
date added to LUP
2016-04-01 15:33:23
date last changed
2020-01-12 18:34:17
@article{47938515-1216-4076-bac7-b7abfb9d0dab,
  abstract     = {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.},
  author       = {Westin, Jenny and Lindgren, Hanna and Gardi, Jonathan and Nyengaard, Jens Randel and Brundin, Patrik and Mohapel, Paul and Cenci Nilsson, Angela},
  issn         = {1529-2401},
  language     = {eng},
  number       = {37},
  pages        = {9448--9461},
  publisher    = {Society for Neuroscience},
  series       = {J Neurosci},
  title        = {Endothelial proliferation and increased blood-brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0944-06.2006},
  doi          = {10.1523/JNEUROSCI.0944-06.2006},
  volume       = {26},
  year         = {2006},
}