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Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain.

Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain. Research Abstract Details 

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  • Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain. Abstract Text:

    jae k ryuJae K Ryu,james g mclarnonJames G McLarnon,jae k ryuJae K Ryu,james g mclarnonJames G McLarnon,jae k ryuJae K Ryu,james g mclarnonJames G McLarnon,

    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.

    Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain. Publishing Authors By Initials

    jk ryuJK Ryu,jg mclarnonJG McLarnon,jk ryuJK Ryu,jg mclarnonJG McLarnon,jk ryuJK Ryu,jg mclarnonJG McLarnon,

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    Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Neurobiology of disease

    VOLUME: 29

    Page Numbers: 254-66

    Journal Abbreviation: Neurobiol. Dis.

    ISSN: 0969-9961

    DAY: 15

    MONTH: 09

    YEAR: 2007

    Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain. Information

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    LANGUAGE: eng

    NlmUniqueID: 9500169

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    Grant and Affiliation Information for Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain.

    AFFILIATION: Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Neurobiol Dis

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