title: Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington's disease.
abstract: OBJECTIVE
  3-Nitropropionic acid (3-NPA) is a natural toxin that, when administered to experimental animals, reproduces the brain lesions observed in Huntington's disease, which mainly consist of selective neurodegeneration of the striatum. The lesions also include severe alterations to the blood-brain barrier (BBB), which increase its permeability to several substances including blood components and exogenous fluorescent dyes, and the concomitant degradation of some of its constituents such as endothelial cells, tight junction proteins and the basement membrane. We studied here the role of matrix metalloproteinases (MMPs)-2 and -9, also called gelatinases A and B, in the degradation of the BBB in the striatal lesions induced by the systemic administration of 3-NPA to Sprague-Dawley rats.
  
  
  METHODS
  3-NPA was intraperitoneally administered at a dose of 20 mg/kg once a day for 3 days. MMPs were studied by means of immunohistochemistry and in situ zymography.
  
  
  RESULTS
  In 3-NPA-treated rats, MMP-9 was present in most of the degraded blood vessels in the injured striatum, while it was absent in vessels from non-injured tissue. In the same animals, MMP-2 staining was barely detected close to degraded blood vessels. The combination of MMP-9 immunostaining, in situ zymography and inhibitory studies of MMP-9 confirmed that net gelatinolytic activity detected in the degraded striatal blood vessels could be attributed almost exclusively to the active form of MMP-9.
  
  
  CONCLUSIONS
  Our results highlight the prominent role of MMP-9 in BBB disruption in the striatal injured areas of this experimental model of Huntington's disease.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Duran-Vilaregut
authors.forename: J
authors.initials: J
authors.lastname: del Valle
authors.forename: G
authors.initials: G
authors.lastname: Manich
authors.forename: A
authors.initials: A
authors.lastname: Camins
authors.forename: M
authors.initials: M
authors.lastname: Pallàs
authors.forename: J
authors.initials: J
authors.lastname: Vilaplana
authors.forename: C
authors.initials: C
authors.lastname: Pelegrí
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D020780:Matrix Metalloproteinase 9; C015392:3-nitropropionic acid