Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain.
Neurobiol Dis
; 29(2): 254-66, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-17964176
ABSTRACT
Injection of Abeta(1-42) peptide into rat hippocampus has been found to induce microglial reactivity and perturbed vasculature in an animal model of inflamed Alzheimer's disease (AD) brain. We report the anti-angiogenic and anti-inflammatory compound, thalidomide, to significantly inhibit peptide-induced vascular changes including endothelial cell proliferation (marker rat endothelial cell antigen-1, RECA-1), angiogenic activity (marker laminin) and leakiness of blood-brain barrier (BBB, marker albumin). Thalidomide also blocked microgliosis and astrogliosis with double immunostaining showing considerable regions of association of activated microglia with vascular remodeling and leaky BBB. Thalidomide inhibition of the glial-derived proinflammatory/angiogenic factor TNF-alpha (tumor necrosis factor-alpha) in Abeta(1-42)-injected brain and also in vitro from peptide-activated human microglia could underly the changes in vascular processes. Thalidomide treatment in vivo was also associated with a significant reduction in hippocampal neuronal loss. Our findings suggest altered cerebral vasculature as an integral component of inflammatory responses with thalidomide an effective inhibitor of gliosis, vascular changes and TNF-alpha leading to neuroprotection in an animal model of inflamed AD brain.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Talidomida
/
Encéfalo
/
Fator de Necrose Tumoral alfa
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Inibidores da Angiogênese
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Células Endoteliais
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA