title: Experimental Induction of Cerebral Aneurysms by Developmental Low Copper Diet.
abstract: Optimal models are needed to understand the pathophysiology of human cerebral aneurysms (CA). We investigated the development of experimental CA by decreasing the activity of lysyl oxidases by dietary copper deficiency from the time of gestation and then augmenting vascular stress by angiotensin II infusion in adulthood. Rats were fed copper-free, low-copper, or normal diets at different time periods from gestation to adulthood. The incidences of CAs were evaluated and autopsies performed to determine the coexistence of cardiovascular diseases. A copper-free diet from gestation was associated with high mortality rates (79.1%) resulting from rupture of ascending aorta aneurysms; a low-copper diet led to acceptable mortality rates (13.6%) and produced CAs and subarachnoid hemorrhage in 46.4% and 3.6% of animals, respectively. Higher proportions of CAs (up to 33.3%) in the rats primed for copper deficiency from gestation ruptured following angiotensin II infusion from adulthood. Gene expression array analyses of the CAs indicated that genes involving extracellular matrix and vascular remodeling were altered in this model. This model enables future research to understand the entire pathogenetic basis of CA development and rupture in association with systemic vasculopathies.
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Shin
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Keon-Joo
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Soyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR).
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea (KHJ, KC, STL, YWS, KJL, DKP, JSY, SK, MK, SKL, JKR); Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea (KHJ, KC, STL, MK, SKL); and Department of Neurology, Armed Forces Capital Hospital, Seongnam, Gyeunggido, South Korea (JKR). rohjk777@gmail.com.
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003300:Copper / Q000008:administration & dosage* / Q000172:deficiency*; D005260:Female; D002532:Intracranial Aneurysm / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003300:Copper
keywords: Angiotensin II; Animal model; Aortic aneurysm; Cerebral aneurysm; Copper; Lysyl oxidase.