期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 30, 期 1, 页码 162-176出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2009.206
关键词
Alzheimer's disease; amyloid-beta; Evans blue albumin; glucose; lactate; perivascular fluid flow
资金
- Alzheimer's Association [IIRG-06-26022]
- NIH [NS36728, NS047546]
- College of Medicine, University of Arkansas for Medical Sciences
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P30NS047546, R01NS036728] Funding Source: NIH RePORTER
Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-C-14] glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-C-14] glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss. Brief infusion of [1-C-14] glucose and D-[C-14] lactate into the inferior colliculus of conscious rats during acoustic stimulation labeled the meninges, consistent with perivascular clearance of [C-14] metabolites from interstitial fluid. Microinfusion of Evans blue albumin and amyloid-beta(1-40) (A beta) caused perivascular labeling in the inferior colliculus, labeled the surrounding meninges, and A beta-labeled-specific blood vessels in the caudate and olfactory bulb and was deposited in cervical lymph nodes. Efflux of extracellular glucose, lactate, and A beta into perivascular fluid pathways is a normal route for clearance of material from the inferior colliculus that contributes to underestimates of brain energetics. Convergence of 'watershed' drainage to common pathways may facilitate perivascular amyloid plaque formation and pathway obstruction in Alzheimer's disease. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 162-176; doi: 10.1038/jcbfm.2009.206; published online 30 September 2009
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