4.6 Article

Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria

Journal

MICROBES AND INFECTION
Volume 12, Issue 14-15, Pages 1198-1207

Publisher

ELSEVIER
DOI: 10.1016/j.micinf.2010.08.006

Keywords

Plasmodium berghei ANKA; Object recognition; Spatial memory; Motor coordination; Brain pathology; Chloroquine treatment

Funding

  1. NTH Training Grant in Mechanisms of Cardiovascular Diseases [T32 HL-07675]
  2. Albert Einstein College of Medicine
  3. Burroughs-Wellcome Fund's Career Awards for Medical Scientists
  4. Einstein-Montefiore Institute for Clinical and Translational Research Career Development [AI076248, AI39454, NS041282]

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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. Published by Elsevier Masson SAS on behalf of the Institut Pasteur.

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