Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid

被引：19
作者：
Duran-Vilaregut, Joaquim [1 ]
del Valle, Jaume [1 ]
Camins, Antoni [2 ]
Pallas, Merce [2 ]
Pelegri, Carme [1 ]
Vilaplana, Jordi [1 ]
机构：
[1] Univ Barcelona, Fac Farm, Dept Fisiol, E-08028 Barcelona, Spain
[2] Univ Barcelona, Inst Biomed IBUB, Fac Farm, Unitat Farmacol & Farmacognosia, E-08028 Barcelona, Spain
来源：
NEUROTOXICOLOGY | 2009年 / 30卷 / 01期
关键词：
3-Nitropropionic acid; Blood-brain barrier; Huntington's disease; Evans blue; Striatum; CEREBRAL ENDOTHELIAL-CELLS; HUNTINGTONS-DISEASE; MITOCHONDRIAL TOXIN; OXIDATIVE STRESS; FOCAL ISCHEMIA; LESIONS; GLUTAMATE; EXPRESSION; RECEPTORS; TOXICITY;
D O I：
10.1016/j.neuro.2008.10.007
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
3-Nitropropionic acid (3-NPA) is a natural toxin that is used to induce models of Huntington's disease (HD) in experimental animals. Here we injected 3-NPA into Sprague-Dawley rats in order to evaluate its effects on the blood-brain barrier (BBB). Evans blue (EB) extravasation was used to identify injured areas in the brains of the treated animals and immunostainings of endothelial brain barrier antigen (EBA), zona occludens-1 (ZO-1) and laminin were used as markers to characterize the effects of the neurotoxin on the BBB. Treated rats had a significant loss of body weight compared to controls, and a correlation between motor affectation and body weight loss was observed in the former. The lateral part of the striatum was specifically injured in treated animals and the BBB almost disappeared in the core of the injured areas, as evidenced by a high EB extravasation and severe alterations of the immunostainings of the three BBB integrity markers compared to those of control animals. We conclude that the BBB is severely affected in the 3-NPA rat model of HD and that disruption of this barrier is a crucial event during the development of this disease. (C) 2008 Elsevier Inc. All rights reserved.
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收藏
页码：136 / 143
页数：8
相关论文
共 54 条
[1]   Differential involvement of cell cycle reactivation between striatal and cortical neurons in cell death induced by 3-nitropropionic acid [J].
Akashiba, Hiroki ;
Ikegaya, Yuji ;
Nishiyama, Nobuyoshi ;
Matsuki, Norio .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (10) :6594-6606
[2]   Extracellular matrix, junctional integrity and matrix metalloproteinase interactions in endothelial permeability regulation [J].
Alexander, JS ;
Elrod, JW .
JOURNAL OF ANATOMY, 2002, 200 (06) :561-574
[3]   Metabolic compromise with systemic 3-nitropropionic acid produces striatal apoptosis in Sprague-Dawley rats but not in BALB/c ByJ mice [J].
Alexi, T ;
Hughes, PE ;
Knüsel, B ;
Tobin, AJ .
EXPERIMENTAL NEUROLOGY, 1998, 153 (01) :74-93
[4]   3-NITROPROPIONATE, TOXIC SUBSTANCE OF INDIGOFERA, IS A SUICIDE INACTIVATOR OF SUCCINATE-DEHYDROGENASE - (RAT-LIVER MITOCHONDRIA CARBANION-N-5 FLAVIN ADDUCTS 2-PROTON ABSTRACTION MECHANISM) [J].
ALSTON, TA ;
MELA, L ;
BRIGHT, HJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (09) :3767-3771
[5]   The NMDA and AMPA/KA receptors are involved in glutamate-induced alterations of occludin expression and phosphorylation in brain endothelial cells [J].
Andras, Ibolya E. ;
Deli, Maria A. ;
Veszelka, Szilvia ;
Hayashi, Kentaro ;
Hennig, Bernhard ;
Toborek, Michal .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2007, 27 (08) :1431-1443
[6]   Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia [J].
Asahi, M ;
Wang, XY ;
Mori, T ;
Sumii, T ;
Jung, JC ;
Moskowitz, MA ;
Fini, ME ;
Lo, EH .
JOURNAL OF NEUROSCIENCE, 2001, 21 (19) :7724-7732
[7]  
BEAL MF, 1993, J NEUROSCI, V13, P4181
[8]   Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II [J].
Benchoua, Alexandra ;
Trioulier, Yael ;
Diguet, Elsa ;
Malgorn, Carole ;
Gaillard, Marie-Claude ;
Dufour, Noelle ;
Elalouf, Jean-Marc ;
Krajewski, Stan ;
Hantraye, Philippe ;
Deglon, Nicole ;
Brouillet, Emmanuel .
HUMAN MOLECULAR GENETICS, 2008, 17 (10) :1446-1456
[9]   The effects of perinatal hypoxia on the behavioral, neurochemical, and neurohistological toxicity of the metabolic inhibitor 3-nitropropionic acid [J].
Binienda, Z ;
Frederick, DL ;
Ferguson, SA ;
Rountree, RL ;
Paule, MG ;
Schmued, L ;
Ali, SF ;
Slikker, W ;
Scallet, AC .
METABOLIC BRAIN DISEASE, 1995, 10 (04) :269-282
[10]   3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease [J].
Brouillet, E ;
Jacquard, C ;
Bizat, N ;
Blum, D .
JOURNAL OF NEUROCHEMISTRY, 2005, 95 (06) :1521-1540
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