Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria |
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| Authors: | Minxian Dai Sandra E. Reznik David C. Spray Louis M. Weiss Herbert B. Tanowitz Maria Gulinello Mahalia S. Desruisseaux |
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| Affiliation: | 1. Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St Johns University, Queens, NY 11439, USA;2. The Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA;3. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA;4. Department of Pathology, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Forchheimer 504, Bronx, NY 10461, USA;5. Behavioral Core Facility, Albert Einstein College of Medicine, Bronx, NY 10461, USA;1. Center for Infection and Immunity of Lille, CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, Lille, France;2. Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Canada;3. Imaging Platform, Research Pole, Lille University Hospital, Lille, France;4. Université de Lille, UDSL, EA 1046 Lille, France;1. University of New Mexico, Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;2. Department of Medical Biochemistry, Maseno University, Maseno, Kenya;3. Center for Global Health, University of New Mexico, Albuquerque, NM, USA;4. Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;5. Department of Psychology, College of Charleston, Charleston, SC, USA;1. Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK;2. Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, University of Copenhagen and Department of Infectious Diseases, Rigshospitalet, 1017 Copenhagen, Denmark;3. Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark;4. National Institute for Medical Research, Tanga, 2448 Ocean Road, P.O. Box 9653, Dar es Salaan, Tanzania;1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India;2. Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India |
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| Abstract: | Human cerebral malaria causes neurological and behavioral deficits which persist long after resolution of infection and clearance of parasites with antimalarial drugs. Previously, we demonstrated that during active infection, mice with cerebral malaria demonstrated negative behavioral outcomes. Here we used a chloroquine treatment model of cerebral malaria to determine whether these abnormal outcomes would be persistent in the mouse model. C57BL/6 mice were infected with Plasmodium berghei ANKA, and treated for ten days. After cessation of chloroquine, a comprehensive assessment of cognitive and motor function demonstrated persistence of abnormal behavioral outcomes, 10 days after successful eradication of parasites. Furthermore, these deficits were still evident forty days after cessation of chloroquine, indicating persistence long after successful treatment, a hallmark feature of human cerebral malaria. Thus, cognitive tests similar to those used in these mouse studies could facilitate the development of adjunctive therapies that can ameliorate adverse neurological outcomes in human cerebral malaria. |
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