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Brain region- and metal-specific effects of embedded metals in a shrapnel wound model in the rat
Affiliation:1. Risk Sciences International, 251 Laurier Avenue West, Suite 700, Ottawa, ON, Canada;2. School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada;3. European Aluminium Association, Brussels, Belgium;4. International Aluminium Institute, London, United Kingdom;5. Occupational Health Program, Faculty of Medicine, McGill University, Montreal, QC, Canada;6. McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada;1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland;2. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland;3. Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland;4. Department of Radiation Oncology, Johns Hopkins University, School of Medicine, Baltimore, Maryland;6. Department of Neurology, Dalian Municipal Central Hospital, Dalian, Liaoning, China;1. Brain, Behavior & the Environment Program, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL 33199, United States;2. Department of Environmental Health Sciences, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL 33199, United States;3. Department of Biostatistics, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL 33199, United States;1. Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital/Center, No. 519 Kunzhou Road, Xishan District, Kunming 650118, Yunnan, PR China;2. Department of Second Urology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan, PR China;3. Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital/Center, No. 519 Kunzhou Road, Xishan District, Kunming 650118, Yunnan, PR China;4. Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital/Center, No. 519 Kunzhou Road, Xishan District, Kunming 650118, Yunnan, PR China;1. Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland;2. Division of Neuroradiology, Kantonsspital Aarau, Aarau, Switzerland
Abstract:The health effects of prolonged exposure to embedded metal fragments, such as those found in shrapnel wounds sustained by an increasing number of military personnel, are not well known. As part of a large collaborative effort to expand this knowledge, we use an animal model of shrapnel wounds originally developed to investigate effects of embedded depleted uranium to investigate effects of military-relevant metals tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium compared to an inert control, tantalum. Rats are surgically implanted with pellets of one of the metals of interest in the gastrocnemius (leg) muscle and tracked until 1 month, 3 months, 6 months, or 12 months from the time of implant, at which point they are euthanized and multiple organs and tissue samples are collected for inspection. Here we focus on four regions of the brain: frontal cortex, hippocampus, amygdala, and cerebellum. We examined changes in accumulated metal concentration in each region as well as changes in expression of proteins related to blood brain barrier tight junction formation, occludin and ZO-1, and synapse function, PSD95, spinophilin, and synaptotagmin. We report few changes in metal accumulation or blood brain barrier protein expression, but a large number of synapse proteins have reduced expression levels, particularly within the first 6 months of exposure, but there are regional and metal-specific differences in effects.
Keywords:Brain  Frontal cortex  Hippocampus  Amygdala  Cerebellum  Rat  Embedded metal  Shrapnel
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