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Evaluation of chronic lead effects in the blood brain barrier system by DCE-CT
Institution:1. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202, United States;2. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, United States;3. School of Health Sciences, Purdue University, West Lafayette, IN, 47907, United States;1. Clinical Medical College, Dali University, Dali, Yunnan, China;2. Affiliated Hospital of Guizhou Medical University, Guiyang, China;3. Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China;4. Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China;1. Institute for Environmental Studies, Charles University in Prague, Benátská 2, Prague, CZ-12801, Czech Republic;2. Institute of Soil Biology and SoWa Research Infrastructure, Biology Centre, Czech Academy of Sciences, Na Sádkách 7, ?eské Budějovice, CZ-37005, Czech Republic;1. Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany;2. Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany;1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba 260-8675, Japan;2. Surface and Nano Analysis Research Group, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, 1-1-1 Higashi Tsukuba, Ibaraki 305-8565, Japan;3. Department of Applied Chemistry, School of Engineering, Tokyo Denki University, 5 Senju-Asahi-cho, Adachi, Tokyo 120-8551, Japan
Abstract:BackgroundLead (Pb) is an environmental factor has been suspected of contributing to the dementia including Alzheimer’s disease (AD). Our previous studies have shown that Pb exposure at the subtoxic dose increased brain levels of beta-amyloid (Aβ) and amyloid plaques, a pathological hallmark for AD, in amyloid precursor protein (APP) transgenic mice, and is hypothesized to inhibit Aβ clearance in the blood- cerebrospinal fluid (CSF) barrier. However, it remains unclear how different levels of Pb affect Aβ clearance in the whole blood-brain barrier system. This study was designed to investigate whether chronic exposure of Pb affected the permeability of the blood-brain barrier system by using the Dynamic Contrast-Enhanced Computerized Tomography (DCE-CT) method.MethodsDEC-CT was used to investigate whether chronic exposure of toxic Pb affected the permeability of the real-time blood brain barrier system.ResultsData showed that Pb exposure increased permeability surface area product, and also significantly induced brain perfusion. However, Pb exposure did not alter extracellular volumes or fractional blood volumes of mouse brain.ConclusionOur data suggest that Pb exposure at subtoxic and toxic levels directly targets the brain vasculature and damages the blood brain barrier system.
Keywords:Lead  Alzheimer’s disease  Beta amyloid  DCE-CT  Permeability  APP transgenic mice
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