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BioMed Research International
Volume 2015, Article ID 937148, 12 pages
http://dx.doi.org/10.1155/2015/937148
Research Article

Histamine Induces Alzheimer’s Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

1Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA
2Department of Cell Biology, Rowan School of Osteopathic Medicine, Stratford, NJ 08084, USA
3Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA
4Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA

Received 21 August 2015; Revised 30 October 2015; Accepted 8 November 2015

Academic Editor: Wiep Scheper

Copyright © 2015 Jonathan C. Sedeyn et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Among the top ten causes of death in the United States, Alzheimer’s disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD.