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Distribution of intraventricularly administered antiamyloid-beta peptide (Aβ) antibody in the mouse brain

Authors

  • Neelima B. Chauhan,

    1. Department of Neuroscience, Finch University of Health Sciences, The Chicago Medical School, North Chicago, Illinois
    2. Neurology Service, Edward Hines, Jr., VA Hospital, Hines, Illinois
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  • George J. Siegel,

    Corresponding author
    1. Neurology Service, Edward Hines, Jr., VA Hospital, Hines, Illinois
    2. Departments of Neurology and of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois
    • Neurology Service (127), Hines VA Hospital, Hines, IL 60141
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  • Terry Lichtor

    1. Department of Neurological Surgery, Rush University Medical Center, Chicago, Illinois
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

There is considerable interest in utilizing the intracerebroventricular (icv) route of administration of antibodies in the brain for various studies and for the therapy of malignancies, but very little is known about the anatomic extent of distribution of the antibody in brain after injection into the third ventricle. To explore the potential for icv administration of antiamyloid-beta peptide (Aβ) in reducing Aβ toxicity in brain in Alzheimer's disease, we first mapped the time course and path of transit of horseradish peroxidase (HRP)-labeled antibody. The results show that, after a single injection into the mouse third venticle, the HRP-labeled antibody is localized within the microvasculature, first that of the corticohippocampal region close to the site of injection at 3 hr. By 24 hr, the antibody is distributed throughout the hippocampus and frontoparietal cortex close to the injection site, as well as in the deep and outer cerebral cortex and cerebellar cortex remote from the injection site. The injected antibody is almost entirely removed by 4 days. Therefore, the antibody had diffused throughout all the brain by 24 hr, showing the feasibility of small quantities of anti-Aβ antibody infused into the third ventricle to reach extracellular epitopes throughout the brain parenchyma rapidly. J. Neurosci. Res. 66:231–235, 2001. Published 2001 Wiley-Liss, Inc.

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