TY - JOUR
T1 - Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington's disease
AU - Duran-Vilaregut, J.
AU - del Valle, J.
AU - Manich, G.
AU - Camins, A.
AU - Pallàs, M.
AU - Vilaplana, J.
AU - Pelegrí, Carme
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - 3-nitropropionic acid
KW - Blood-brain barrier
KW - Huntington's disease
KW - Immunohistochemistry
KW - Matrix metallopro teinase
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=79960263505&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2990.2010.01157.x
DO - 10.1111/j.1365-2990.2010.01157.x
M3 - Artículo
C2 - 21175737
AN - SCOPUS:79960263505
VL - 37
SP - 525
EP - 537
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
SN - 0305-1846
IS - 5
ER -