Suppression of clinical signs of cell-transferred experimental allergic encephalomyelitis and altered cerebrovascular permeability in Lewis rats treated with a plasminogen activator inhibitor |
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| Authors: | C S Koh P Y Paterson |
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| Institution: | 1. Department of Microbiology-Immunology, The Medical and Dental Schools, Northwestern University, Chicago, Illinois 60611, U.S.A.;2. Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60201 U.S.A.;1. School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, PR China;2. Department of Bioengineering, University of Illinois at Chicago, Chicago 60607, United States;1. Department of Neuroinfection and Neuroimmunology, Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Capital Medical University, No.119 South 4thRing West Road, Fengtai District, Beijing 100160, China;2. Department of Neurology, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Xicheng District, Beijing 100053, China;3. Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China;1. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China;2. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, PR China;3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China;1. Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan;2. Department of Neurology, Tohoku University School of Medicine, Sendai, Japan;3. Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan;4. Keio Advanced Research Center for Water Biology and Medicine, Keio University, Tokyo, Japan;5. Department Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China;6. Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China;7. Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China;8. Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan |
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| Abstract: | The purpose of this study was to determine whether fibrinolysis resulting from activation of the clotting cascade in juxtaposition to endothelial cells of the central nervous system (CNS) microvasculature is important for development of clinical signs of experimental allergic encephalomyelitis (EAE) in recipient Lewis rats. Rats were injected with previously primed syngeneic lymph node cells, activated in vitro with guinea pig myelin basic protein, and subsequently treated daily with trans-4-(aminomethyl)cyclohexanecarboxylic acid (AMCA), a synthetic inhibitor of plasminogen activator. Clinical signs of EAE were significantly suppressed in AMCA-treated rats compared to saline-treated control recipient animals. Furthermore, suppression of clinical signs in AMCA-treated rats was accompanied by a significant curtailment in EAE-associated increased permeability of the blood-brain barrier (BBB). These findings provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of the BBB, are related prerequisite events for expression of clinical manifestations of EAE. |
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