Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

Jian Ming Li, Yan Cai, Fei Liu, La Yang, Xia Hu, Peter R. Patrylo, Huaibin Cai, Xue Gang Luo, Dong Xiao, Xiao Xin Yan

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

    Original languageEnglish (US)
    Pages (from-to)10772-10785
    Number of pages14
    JournalOncotarget
    Volume6
    Issue number13
    DOIs
    StatePublished - 2015

    Keywords

    • Alzheimer's disease
    • Amyloid pathology
    • Axonal pathology
    • Brain aging
    • Silent stroke

    ASJC Scopus subject areas

    • Oncology

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