Oncotarget

Research Papers: Pathology:

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

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

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Oncotarget. 2015; 6:10772-10785. https://doi.org/10.18632/oncotarget.3599

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Abstract

Jian-Ming Li1,2, Yan Cai1, Fei Liu3, La Yang2, Xia Hu1, Peter R. Patrylo4, Huaibin Cai5, Xue-Gang Luo1, Dong Xiao6 and Xiao-Xin Yan1

1 Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China

2 Neuroscience Research Center, Changsha Medical University, Changsha, Hunan, China

3 Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

4 Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University School of Medicine, Carbondale, Illinois, USA

5 Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA

6 State Key Laboratory of Coal Resources and Safe Mining, China University of Mining and Technology, Xuzhou, Jiangsu, China

Correspondence to:

Xiao-Xin Yan, email:

Keywords: Alzheimer’s disease, amyloid pathology, axonal pathology, brain aging, silent stroke

Received: January 21, 2015 Accepted: February 20, 2015 Published: March 14, 2015

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.


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