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• W2029881431 abstract "Abstract This study has used immunohistochemical examination of tissue obtained from Alzheimer’s disease (AD) brains and rat hippocampus injected with Aβ 1‐42 peptide to determine effects of induced inflammatory reactivity on integrity of blood–brain barrier (BBB) and viability of neurons. Tissue from AD, but not non‐demented, brains exhibited a diffuse pattern of staining for fibrinogen and immunoglobulin (IgG) indicative of BBB leakiness with considerable fibrinogen immunoreactivity (ir) appearing in association with Aβ deposits. Immunostaining for the endothelial cell specific glycoprotein, von Willebrand factor, showed morphological evidence for altered blood vessels in AD tissue. AD brains also demonstrated extensive areas of fibrinogen ir in association with microglial reactivity. In vivo, intra‐hippocampal injection of Aβ 1‐42 caused time‐dependent (1–7 days after injection) increases in double staining of fibrinogen with areas of microgliosis. Two independent pharmacological strategies were employed to examine how Aβ 1‐42 stimulation (7 days injection) may be linked to neurodegeneration. The defibrinogenating compound, ancrod, reduced inflammatory reactivity, levels of parenchymal fibrinogen and IgG, and was neuroprotective. These results prompted use of Aβ 1‐42 plus fibrinogen as a novel in vivo inflammatory stimulus and this combination significantly enhanced inflammatory reactivity, vascular perturbations and neuronal damage compared to Aβ 1‐42 alone. A second approach, using anti‐Mac‐1 (antibody for antigen CD11b) to block activation of microglia, was highly effective in attenuating effects of Aβ 1‐42 plus fibrinogen amplification of inflammatory and vascular responses and conferred significant neuroprotection. The overall findings from study of AD tissue and in vivo in Aβ 1‐42 and Aβ 1‐42 plus fibrinogen stimulated rat hippocampus suggest microglial responses to promote increased extravasation of blood protein as a critical component in amplifying inflammatory reactivity and causing neuronal damage in inflamed AD brain." @default.
• W2029881431 created "2016-06-24" @default.
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• W2029881431 date "2009-09-01" @default.
• W2029881431 modified "2023-10-16" @default.
• W2029881431 title "A leaky blood-brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer’s disease brain" @default.
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• W2029881431 doi "https://doi.org/10.1111/j.1582-4934.2008.00434.x" @default.
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