Blood-brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons

被引：111

作者：

Rite, Inmaculada ^{[1
]}

Machado, Alberto ^{[1
]}

Cano, Josefina ^{[1
]}

Venero, Jose L. ^{[1
]}

机构：

[1] Univ Seville, Fac Farm, Dept Bioquim Bromatol Toxicol & Med Legal, E-41012 Seville, Spain

来源：

JOURNAL OF NEUROCHEMISTRY | 2007年 / 101卷 / 06期

关键词：

apoptosis; microglia activation; Parkinson's disease; tyrosine hydroxylase loss; vascular endothelial growth factor; ventral mesencephalon;

D O I：

10.1111/j.1471-4159.2007.04567.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson's disease. Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood-brain barrier (BBB) permeability. A single dose of 1 mu g of VEGF, chosen from a dose-response study, highly disrupted the BBB in the ventral mesencephalon in a time-dependent manner. A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase-positive neurons was evident. Moreover, Fluoro-Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL-positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption. We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.

引用

页码：1567 / 1582

页数：16

共 68 条

[1] Ischaemic brain oedema [J].

Ayata, C ;

Ropper, AH .

JOURNAL OF CLINICAL NEUROSCIENCE, 2002, 9 (02) :113-124

[2] Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease [J].

Banati, RB ;

Daniel, SE ;

Blunt, SB .

MOVEMENT DISORDERS, 1998, 13 (02) :221-227

[3] Changes in vascularization in substantia nigra pars compacta of monkeys rendered parkinsonian [J].

Barcia, C ;

Bautista, V ;

Sánchez-Bahillo, A ;

Fernández-Villalba, E ;

Faucheux, B ;

Poza, MPY ;

Barreiro, AF ;

Hirsch, EC ;

Herrero, MT .

JOURNAL OF NEURAL TRANSMISSION, 2005, 112 (09) :1237-1248

[4] Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients [J].

BlumDegen, D ;

Muller, T ;

Kuhn, W ;

Gerlach, M ;

Przuntek, H ;

Riederer, P .

NEUROSCIENCE LETTERS, 1995, 202 (1-2) :17-20

[5] Head trauma preceding PD - A case-control study [J].

Bower, JH ;

Maraganore, DM ;

Peterson, BJ ;

McDonnell, SK ;

Ahlskog, JE ;

Rocca, WA .

NEUROLOGY, 2003, 60 (10) :1610-1615

[6] Vascular endothelial growth factor and the nervous system [J].

Brockington, A ;

Lewis, C ;

Wharton, S ;

Shaw, PJ .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2004, 30 (05) :427-446

[7] Thrombin induces in vivo degeneration of nigral dopaminergic neurones along with the activation of microglia [J].

Carreño-Müller, E ;

Herrera, AJ ;

de Pablos, RM ;

Tomás-Camardiel, M ;

Venero, JL ;

Cano, J ;

Machado, A .

JOURNAL OF NEUROCHEMISTRY, 2003, 84 (05) :1201-1214

[8] 6-Hydroxydopamine-induced alterations in blood-brain barrier permeability [J].

Carvey, PM ;

Zhao, CH ;

Hendey, B ;

Lum, H ;

Trachtenberg, J ;

Desai, BS ;

Snyder, J ;

Zhu, YG ;

Ling, ZD .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 22 (05) :1158-1168

[9] An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration [J].

Cassarino, DS ;

Bennett, JP .

BRAIN RESEARCH REVIEWS, 1999, 29 (01) :1-25

[10]

Castaño A, 1998, J NEUROCHEM, V70, P1584

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