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Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120 : Mechanistic and Therapeutic Implications
Joint Authors
Strayer, David S.
Louboutin, Jean-Pierre
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-02-01
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Medicine
Information Technology and Computer Science
Abstract EN
The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain.
We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model.
Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents.
Gp120 was directly toxic to brain endothelial cells.
Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs).
These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae.
MMP-2 and MMP-9 were upregulated following gp120-injection.
Gp120 reduced laminin and tight junction proteins.
Reactive oxygen species (ROS) activate MMPs.
Injecting gp120 induced lipid peroxidation.
Gene transfer of antioxidant enzymes protected against gp120-induced BBB abnormalities.
NMDA upregulates the proform of MMP-9.
Using the NMDA receptor (NMDAR-1) inhibitor, memantine, we observed partial protection from gp120-induced BBB injury.
Thus, (1) HIV-envelope gp120 disrupts the BBB; (2) this occurs via lesions in brain microvessels, MMP activation and degradation of vascular basement membrane and vascular tight junctions; (3) NMDAR-1 activation plays a role in this BBB injury; and (4) antioxidant gene delivery as well as NMDAR-1 antagonists may protect the BBB.
American Psychological Association (APA)
Louboutin, Jean-Pierre& Strayer, David S.. 2012. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120 : Mechanistic and Therapeutic Implications. The Scientific World Journal،Vol. 2012, no. 2012, pp.1-15.
https://search.emarefa.net/detail/BIM-475113
Modern Language Association (MLA)
Louboutin, Jean-Pierre& Strayer, David S.. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120 : Mechanistic and Therapeutic Implications. The Scientific World Journal No. 2012 (2012), pp.1-15.
https://search.emarefa.net/detail/BIM-475113
American Medical Association (AMA)
Louboutin, Jean-Pierre& Strayer, David S.. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120 : Mechanistic and Therapeutic Implications. The Scientific World Journal. 2012. Vol. 2012, no. 2012, pp.1-15.
https://search.emarefa.net/detail/BIM-475113
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-475113