Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington's disease

J. Duran-Vilaregut, J. del Valle, G. Manich, A. Camins, M. Pallàs, J. Vilaplana, Carme Pelegrí*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

Abstract

Aim: 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 20mg/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. Conclusion: 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.

Original languageAmerican English
Pages (from-to)525-537
Number of pages13
JournalNeuropathology and Applied Neurobiology
Volume37
Issue number5
DOIs
Publication statusPublished - Aug 2011

Keywords

  • 3-nitropropionic acid
  • Blood-brain barrier
  • Huntington's disease
  • Immunohistochemistry
  • Matrix metallopro teinase
  • Striatum

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