Research Article Histamine Induces Alzheimer’s Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures Jonathan C. Sedeyn, 1 Hao Wu, 1 Reilly D. Hobbs, 2 Eli C. Levin, 1,3 Robert G. Nagele, 3,4 and Venkat Venkataraman 1,2 1 Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA 2 Department of Cell Biology, Rowan School of Osteopathic Medicine, Stratford, NJ 08084, USA 3 Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA 4 Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084, USA Correspondence should be addressed to Venkat Venkataraman; venkatar@rowan.edu Received 21 August 2015; Revised 30 October 2015; Accepted 8 November 2015 Academic Editor: Wiep Scheper Copyright © 2015 Jonathan C. Sedeyn et al. is 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. 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. us, the histamine-treated MBO culture system may provide a valuable tool in combating AD. 1. Introduction As the most common form of dementia, Alzheimer’s dis- ease (AD) is currently affecting over 5.5 million people in the United States and more than 35 million worldwide [1, 2]. e hallmark of the disease is progressive cogni- tive decline that results in loss of language/communication skills, difficulty in learning, loss of memory, and alterations in personality/mood [3–5]. e pathological changes seen in AD include synaptic loss, dendrite retraction, neuronal cell death, inflammation, astrocyte activation, blood-brain barrier (BBB) breakdown, and the accumulation of amyloid peptide 1–42 (A42) within neurons and plaques throughout the hippocampus and cerebral cortex [6–12]. It has been noticed that breakdown of the BBB is a particularly important development in AD progression, as it allows for the leakage of damaging humoral elements into the brain parenchyma [7, 13, 14]. e BBB is comprised of specialized vascular endothelial cells that are connected to one another via tight junctions. ese endothelial cells are different from those in other parts of the mammalian body in that they lack fenestrations and therefore do not allow for free exchange of solutes between the blood and the brain parenchyma [15, 16]. Additionally, astrocytic foot processes wrap around the blood vessels and play an important role in allowing endothelial cells to form and maintain their normally protective, tight seal [17]. When BBB breach occurs in the AD brains, it allows for the extravasation of blood-borne A42, brain-reactive autoantibodies, and inflammatory factors into the normally Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 937148, 12 pages http://dx.doi.org/10.1155/2015/937148