Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid
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 ident...
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Veröffentlicht in: | Neurotoxicology (Park Forest South) 2009, Vol.30 (1), p.136-143 |
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creator | Duran-Vilaregut, Joaquim del Valle, Jaume Camins, Antoni Pallàs, Mercè Pelegrí, Carme Vilaplana, Jordi |
description | 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. |
doi_str_mv | 10.1016/j.neuro.2008.10.007 |
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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.</description><identifier>ISSN: 0161-813X</identifier><identifier>EISSN: 1872-9711</identifier><identifier>DOI: 10.1016/j.neuro.2008.10.007</identifier><identifier>PMID: 19026682</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>3-Nitropropionic acid ; Adult and adolescent clinical studies ; Animals ; Antigens, Surface - analysis ; Basement Membrane - drug effects ; Biological and medical sciences ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Corpus Striatum - blood supply ; Corpus Striatum - pathology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Endothelium, Vascular - drug effects ; Evans blue ; Huntington Disease - chemically induced ; Huntington's disease ; Laminin - analysis ; Male ; Medical sciences ; Membrane Proteins - analysis ; Nervous system (semeiology, syndromes) ; Nervous system as a whole ; Neurology ; Nitro Compounds - toxicity ; Organic mental disorders. Neuropsychology ; Phosphoproteins - analysis ; Propionates - toxicity ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. 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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.</description><subject>3-Nitropropionic acid</subject><subject>Adult and adolescent clinical studies</subject><subject>Animals</subject><subject>Antigens, Surface - analysis</subject><subject>Basement Membrane - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Corpus Striatum - blood supply</subject><subject>Corpus Striatum - pathology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Evans blue</subject><subject>Huntington Disease - chemically induced</subject><subject>Huntington's disease</subject><subject>Laminin - analysis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - analysis</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Nervous system as a whole</subject><subject>Neurology</subject><subject>Nitro Compounds - toxicity</subject><subject>Organic mental disorders. Neuropsychology</subject><subject>Phosphoproteins - analysis</subject><subject>Propionates - toxicity</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Striatum</subject><subject>Tight Junctions - drug effects</subject><subject>Toxicology</subject><subject>Zonula Occludens-1 Protein</subject><issn>0161-813X</issn><issn>1872-9711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LXDEUhoO06PjxCwolm7q705zcj9y76KKKWkHopgVdheQkwQx3bsYkV_HfN-MMdicEAi_Pe87hIeQLsCUw6L6vlpOdY1hyxvqSLBkTB2QBveDVIAA-kUWhoOqhvj8ixymtGINWdMMhOYKB8a7r-YI8XIwhmEpH5SeqVYzeRmp8ivMm-zDRkuZHS1OOXuV5TYOjUeVEc7QqW0NffH6kdTX5HMOmvNLxSBV6c0o-OzUme7b_T8jf66s_l7-qu983t5c_7ypsoM9VK1ivrRMI0HRaO9GIFno3NKLWqLqhBQ5CKCbaRjvknIEBNIjtgE67oa5PyPlubln_NNuU5dontOOoJhvmJDnjQ1myBesdiDGkFK2Tm-jXKr5KYHJrVK7km1G5NboNi9HS-rofP-u1Nf87e4UF-LYHVEI1uqgm9Omd4wBMgGgK92PH2SLjuWiWCb2d0BofLWZpgv_wkH_2m5YZ</recordid><startdate>2009</startdate><enddate>2009</enddate><creator>Duran-Vilaregut, Joaquim</creator><creator>del Valle, Jaume</creator><creator>Camins, Antoni</creator><creator>Pallàs, Mercè</creator><creator>Pelegrí, Carme</creator><creator>Vilaplana, Jordi</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>2009</creationdate><title>Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid</title><author>Duran-Vilaregut, Joaquim ; del Valle, Jaume ; Camins, Antoni ; Pallàs, Mercè ; Pelegrí, Carme ; Vilaplana, Jordi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-5708bef7c1146bbf747518f9473bca69512177a0754bfc2201d1cdcc59cfbf933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>3-Nitropropionic acid</topic><topic>Adult and adolescent clinical studies</topic><topic>Animals</topic><topic>Antigens, Surface - analysis</topic><topic>Basement Membrane - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Corpus Striatum - blood supply</topic><topic>Corpus Striatum - pathology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Evans blue</topic><topic>Huntington Disease - chemically induced</topic><topic>Huntington's disease</topic><topic>Laminin - analysis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - analysis</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Nervous system as a whole</topic><topic>Neurology</topic><topic>Nitro Compounds - toxicity</topic><topic>Organic mental disorders. Neuropsychology</topic><topic>Phosphoproteins - analysis</topic><topic>Propionates - toxicity</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Striatum</topic><topic>Tight Junctions - drug effects</topic><topic>Toxicology</topic><topic>Zonula Occludens-1 Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duran-Vilaregut, Joaquim</creatorcontrib><creatorcontrib>del Valle, Jaume</creatorcontrib><creatorcontrib>Camins, Antoni</creatorcontrib><creatorcontrib>Pallàs, Mercè</creatorcontrib><creatorcontrib>Pelegrí, Carme</creatorcontrib><creatorcontrib>Vilaplana, Jordi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neurotoxicology (Park Forest South)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duran-Vilaregut, Joaquim</au><au>del Valle, Jaume</au><au>Camins, Antoni</au><au>Pallàs, Mercè</au><au>Pelegrí, Carme</au><au>Vilaplana, Jordi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid</atitle><jtitle>Neurotoxicology (Park Forest South)</jtitle><addtitle>Neurotoxicology</addtitle><date>2009</date><risdate>2009</risdate><volume>30</volume><issue>1</issue><spage>136</spage><epage>143</epage><pages>136-143</pages><issn>0161-813X</issn><eissn>1872-9711</eissn><abstract>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.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>19026682</pmid><doi>10.1016/j.neuro.2008.10.007</doi><tpages>8</tpages></addata></record> |
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subjects | 3-Nitropropionic acid Adult and adolescent clinical studies Animals Antigens, Surface - analysis Basement Membrane - drug effects Biological and medical sciences Blood-brain barrier Blood-Brain Barrier - drug effects Corpus Striatum - blood supply Corpus Striatum - pathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Endothelium, Vascular - drug effects Evans blue Huntington Disease - chemically induced Huntington's disease Laminin - analysis Male Medical sciences Membrane Proteins - analysis Nervous system (semeiology, syndromes) Nervous system as a whole Neurology Nitro Compounds - toxicity Organic mental disorders. Neuropsychology Phosphoproteins - analysis Propionates - toxicity Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Rats Rats, Sprague-Dawley Striatum Tight Junctions - drug effects Toxicology Zonula Occludens-1 Protein |
title | Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid |
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