Jens Randel Nyengaard

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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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 E.; Lindgren, Hanna S.; Gardi, Jonathan; Nyengaard, Jens Randel; Brundin, Patrik; Mohapel, Paul; Cenci, M. Angela.

In: Journal of Neuroscience, Vol. 26, No. 37, 13.09.2006, p. 9448-9461.

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Westin, Jenny E. ; Lindgren, Hanna S. ; Gardi, Jonathan ; Nyengaard, Jens Randel ; Brundin, Patrik ; Mohapel, Paul ; Cenci, M. Angela. / Endothelial proliferation and increased blood-brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 37. pp. 9448-9461.

Bibtex

@article{300493672a9b4bdab6edd75253d420db,
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",
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.",
keywords = "6-OHDA, Angiogenesis, Basal ganglia, Blood-brain barrier, BrdU, Dyskinesia, Parkinson's disease, Proliferation",
author = "Westin, {Jenny E.} and Lindgren, {Hanna S.} and Jonathan Gardi and Nyengaard, {Jens Randel} and Patrik Brundin and Paul Mohapel and Cenci, {M. Angela}",
year = "2006",
month = sep,
day = "13",
doi = "10.1523/JNEUROSCI.0944-06.2006",
language = "English",
volume = "26",
pages = "9448--9461",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "37",

}

RIS

TY - JOUR

T1 - Endothelial proliferation and increased blood-brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia

AU - Westin, Jenny E.

AU - Lindgren, Hanna S.

AU - Gardi, Jonathan

AU - Nyengaard, Jens Randel

AU - Brundin, Patrik

AU - Mohapel, Paul

AU - Cenci, M. Angela

PY - 2006/9/13

Y1 - 2006/9/13

N2 - 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.

AB - 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.

KW - 6-OHDA

KW - Angiogenesis

KW - Basal ganglia

KW - Blood-brain barrier

KW - BrdU

KW - Dyskinesia

KW - Parkinson's disease

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=33748711640&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0944-06.2006

DO - 10.1523/JNEUROSCI.0944-06.2006

M3 - Journal article

C2 - 16971529

AN - SCOPUS:33748711640

VL - 26

SP - 9448

EP - 9461

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 37

ER -