Journal
EXPERIMENTAL NEUROLOGY
Volume 198, Issue 2, Pages 552-557Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2005.12.016
Keywords
Alzheimer's disease; blood-brain barrier; astrocytes; amyloid beta-peptide; inflammation; microglia/macrophages; minocycline; 1400W
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This work has examined levels of 3-nitrotyrosine (3-NT, a marker for peroxynitrite formation) and intactness of blood-brain barrier (BBB) in amyloid beta-peptide (A beta(1-42))-injected rat hippocampus. Immunohistochemical analysis demonstrated 3-NT immunoreactivity in microglia/macrophages and astrocytes were significantly increased at 7 days post-A beta(1-42) injection. Administration of the broad spectrum anti-inflammatory agent minocycline or the selective NOS inhibitor 1400W markedly reduced 3-NT levels. Double immunofluorescence staining showed that 3-NT was prominently expressed in microglia/macrophages and astrocytes located in proximity to blood vessels. Additionally, A beta(1-42) injection caused a marked increase in permeability of the BBB to immunoglobulin G (IgG); both minocycline and 1400W were highly effective in decreasing the leakiness of the BBB. Our results suggest the involvement of glial-derived reactive nitrogen species in mediating increased BBB permeability in A beta(1-42) injected rat hippocampus. (C) 2005 Elsevier Inc. All rights reserved.
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