title: Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.
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.
authors: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.|Neuroscience Research Center, Changsha Medical University, Changsha, Hunan, China.
authors: Jian-Ming
authors: JM
authors: Li
authors: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
authors: Yan
authors: Y
authors: Cai
authors: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Fei
authors: F
authors: Liu
authors: Neuroscience Research Center, Changsha Medical University, Changsha, Hunan, China.
authors: La
authors: L
authors: Yang
authors: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
authors: Xia
authors: X
authors: Hu
authors: Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.
authors: Peter R
authors: PR
authors: Patrylo
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
authors: Huaibin
authors: H
authors: Cai
authors: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
authors: Xue-Gang
authors: XG
authors: Luo
authors: State Key Laboratory of Coal Resources and Safe Mining, China University of Mining and Technology, Xuzhou, Jiangsu, China.
authors: Dong
authors: D
authors: Xiao
authors: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
authors: Xiao-Xin
authors: XX
authors: Yan
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D054022:Cerebrum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006168:Guinea Pigs; D020766:Intracranial Embolism / Q000378:metabolism / Q000473:pathology*; D009245:NADH Dehydrogenase; D016501:Neurites / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism; D058225:Plaque, Amyloid; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D010320:Parvalbumins; D050598:Vesicular Glutamate Transport Protein 1; D009245:NADH Dehydrogenase; D002795:Choline O-Acetyltransferase; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; amyloid pathology; axonal pathology; brain aging; pathology