کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3070533 1580734 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-α in an animal model of inflamed Alzheimer’s disease brain
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-α in an animal model of inflamed Alzheimer’s disease brain
چکیده انگلیسی

Injection of Aβ1-42 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-α (tumor necrosis factor-α) in Aβ1-42-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-α leading to neuroprotection in an animal model of inflamed AD brain.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 29, Issue 2, February 2008, Pages 254–266
نویسندگان
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