Journal
JOURNAL OF NEUROSCIENCE METHODS
Volume 138, Issue 1-2, Pages 233-242Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2004.04.026
Keywords
blood-brain barrier permeability; perfused mouse brain; amyloid-beta peptide
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Funding
- NIA NIH HHS [AG 16223] Funding Source: Medline
- NINDS NIH HHS [NS 34467] Funding Source: Medline
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The role of transport exchanges of neuroactive solutes across the blood-brain barrier (BBB) is increasingly recognized. To take full advantage of genetically altered mouse models of neurodegenerative disorders for BBB transport studies, we adapted a brain perfusion technique to the mouse. During a carotid brain perfusion with a medium containing sheep red blood cells and mock plasma, the physiological parameters in the arterial inflow, regional cerebral blood flow (C-14-iodoantipyrine autoradiography), ultrastructural integrity of the tissue, barrier to lanthanum, brain water content, energy metabolites and lactate levels remain unchanged. Amyloid-beta peptides (Abeta) were iodinated by lactoperoxidase method. Non-oxidized mono-iodinated Abeta monomers were separated by HPLC (as confirmed by MALDI-TOF spectrometry) and used in transport measurements. Transport of intact... I-125-Abeta40 across the BBB was time- and concentration-dependent in contrast to negligible C-14-inulin uptake. In 5-6 months old Alzheimer's Tg2576 mice, Abeta40BBB transport was increased by >eight-fold compared to age-matched littermate controls, and was mediated via the receptor for advanced glycation endproducts. We conclude the present arterial brain perfusion method provides strictly controlled environment in cerebral microcirculation suitable for examining transport of rapidly and slowly penetrating molecules across the BBB in normal and transgenic mice. (C) 2004 Elsevier B.V. All rights reserved.
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